RF-3192C and other polyketides from the marine endophytic Aspergillus niger ASSB4: structure assignment and bioactivity investigation
AbstractChemical investigation of the methanolic extract of endophyticAspergillus niger SB4, isolated from the marine algaLaurencia obtuse, afforded the pentacyclic polyketide, RF-3192C (1), the dimeric coumarin orlandin (2), fonsecin B (3), TMC-256A1 (4), cyclo-(Leu-Ala) (5), and cerebroside A (6).The chemical structure of RF-3192C (1) is assigned herein for the first time using 1D/2D NMR and HRESI-MS. Additionally, the revision of the NMR assignments of orlandin (2) was reported herein as well. Investigation of the antimicrobial activities of isolated compounds revealed the high activity of RF-3192C (1) againstPseudomona...
Source: Medicinal Chemistry Research - December 1, 2020 Category: Chemistry Source Type: research

Design and synthesis of nature-inspired chromenopyrroles as potential modulators of mitochondrial metabolism
AbstractChromenopyrrole derivatives with multiple stereocenters and variable ring fusion pattern are found in many natural products and biologically appealing molecules. By employing a build/couple/pair strategy, we have recently reported on the discovery of a serendipitous cascade to access a diverse collection of chromenopyrroles. This protocol features a one-pot cascade that includes the generation of azomethine ylide and intramolecular [3  + 2]-cycloaddition. Phenotypic screening of the developed pilot library enabled the identification of chemical probes that efficiently suppress mitochondrial membrane p...
Source: Medicinal Chemistry Research - November 30, 2020 Category: Chemistry Source Type: research

Design, synthesis and biological evaluation of Schiff ’s base derivatives as multifunctional agents for the treatment of Alzheimer’s disease
AbstractA series of Schiff ’s base derivatives was rationally designed, synthesized, and evaluated as multi-function agents for the treatment of Alzheimer’s disease (AD). The results revealed that compound3b was a novel multifunctional agent. It acted as a highly selective monoamine oxidase-B inhibitor (IC50 = 8.4 nM), which was explained by the docking study. Compound3b also was an antioxidant agent (2.3 eq) and could significantly inhibit self-induced Aβ1-42 aggregation (31.8%). Meanwhile, compound3b was a selective metal chelator and could inhibit Cu2+-induced Aβ1-42 aggregatio...
Source: Medicinal Chemistry Research - November 25, 2020 Category: Chemistry Source Type: research

Thiazole-based and thiazolidine-based protein tyrosine phosphatase 1B inhibitors as potential anti-diabetes agents
AbstractAs a disease closely related to the metabolic syndrome, diabetes has become a public health issue that severely affects many people ’s quality of life. The search for novel anti-diabetic agents remains the cornerstone to control this challenging disease. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin and leptin signaling pathways, has turned out to be a potential target of type II diabetes mellitus (T 2DM) and obesity. In recent years, the development of novel anti-diabetic drugs based on PTP1B inhibitors has captured the attention of many researchers. Thiazole, a five-membered heter...
Source: Medicinal Chemistry Research - November 25, 2020 Category: Chemistry Source Type: research

Indazole scaffold: a generalist for marketed and clinical drugs
AbstractMore and more attention has been paid to the structurally diverse indazole analogs in recent years which are widely present in numerous commercially available drugs. Indazole-containing derivatives are endowed with a broad range of biological properties, such as anti-inflammatory, antibacterial, anti-HIV, antiarrhythmics, antifungal and antitumor activities. This review is a guide for pharmacologists who are in search of valid preclinical/clinical drug compounds where the progress, from 1966 to the present day, of approved marketed drugs containing indazole scaffold is examined. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - November 25, 2020 Category: Chemistry Source Type: research

Antioxidant and acetylcholinesterase inhibition activity of aliphatic and aromatic edaravone derivatives
AbstractAs Alzheimer disease (AD) is a multifactorial condition, it should be tackled with drugs targeting multiple key pathways. A series of aliphatic (2–8) and aromatic (9–15) edaravone derivatives were synthesized, characterized, and evaluated as antioxidant agents using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2 ’-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as well as acetylcholinesterase (AChE) inhibitors. In both antioxidant assays, even though the starting compound edaravone was more active, the best derivative was5 with 50% effective concentration (EC50) of 0.0301 and ...
Source: Medicinal Chemistry Research - November 23, 2020 Category: Chemistry Source Type: research

Synthesis and biological evaluation of novel N -substituted nipecotic acid derivatives with tricyclic cage structures in the lipophilic domain as GABA uptake inhibitors
AbstractA new class of GABA reuptake inhibitors with sterically demanding, highly rigid tricyclic cage structures as the lipophilic domain was synthesized and investigated in regard to their biological activity at the murine GABA transporters (mGAT1 –mGAT4). The construction of these compounds, consisting of nipecotic acid, a symmetric tricyclic amine, and a plain hydrocarbon linker connecting the two subunits via their amino nitrogens, was accomplished via reductive amination of a nipecotic acid derivative with anN-alkyl substituent displaying a terminal aldehyde function with tricyclic secondary amines. The target ...
Source: Medicinal Chemistry Research - November 22, 2020 Category: Chemistry Source Type: research

Biological targets of 92 alkaloids isolated from Papaver genus: a perspective based on in silico predictions
AbstractWith its high level of phytochemical and botanical variability,Papaver genus contains several species with many subspecies yielding more than 170 alkaloids.Papaver species have been used as sedative, hypnotic, analgesic, and antidepressant. The aim of this study is to shed light on the structure –activity relationship of alkaloids isolated fromPapaver genus. All alkaloids isolated fromPapaver genus are listed according to their plant source. We identified the molecular targets of the 92 alkaloids from 10 different types ofPapaver alkaloids (simple isoquinoline, benzylisoquinoline, proaporphine, aporphine, mor...
Source: Medicinal Chemistry Research - November 21, 2020 Category: Chemistry Source Type: research

Simple methods of modification of daunorubicin on the daunosamine nitrogen atom
AbstractModification of daunorubicin on its NH2 moiety is a well-established synthetic approach to obtain novel derivatives of this compound. Moreover, the daunosamine moiety of this antibiotic is considered to be the most sensitive part of a molecule in terms of biological response to chemical transformations. Using simple and effective synthetic techniques, namely, alkylation under phase-transfer catalysis and an amine addition across an activated multiple bond, a series of daunorubicin derivatives retaining the amine functionality have been obtained, which could also be used as potential precursors for further transform...
Source: Medicinal Chemistry Research - November 20, 2020 Category: Chemistry Source Type: research

4-benzylideneisoquinoline-1,3( 2H , 4H )-diones as tyrosyl DNA phosphodiesterase 2 (TDP2) inhibitors
AbstractTyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (Top2) mediated DNA damages, including double-strand breaks (DSBs) that underpin the anticancer mechanism of clinical Top2 poisons such as etoposide (ETP). Inhibition of TDP2 could sensitize cancer cells toward Top2 poisons by increasing Top2 cleavage complex. We have previously identified isoquinoline-1,3-dione as a selective inhibitor type of TDP2. However, the reported structure-activity relationship (SAR) was limited to simple substitutions on the isoquinoline-1,3-dione core. Herein, we report the extended SAR consisting of the synthesis and testin...
Source: Medicinal Chemistry Research - November 19, 2020 Category: Chemistry Source Type: research

Tankyrase inhibitors: emerging and promising therapeutics for cancer treatment
AbstractCancer is a disease portrayed by the uncontrolled growth of irregular cells. Tankyrase, a member of poly(ADP-ribose)polymerase family, mediates Wnt signal transduction and has emerged as a new molecular target for the therapy of different kinds of cancer. Wnt/ β-catenin signaling functions significantly in a wide scope of biological events, such as the upkeep of genomic stability, transcriptional control, energy metabolism, and apoptosis. ADP-ribosylation is a reversible posttranslational modification process that regulates several cellular signaling pat hways in which transferase enzymes such as mono (ADP-rib...
Source: Medicinal Chemistry Research - November 17, 2020 Category: Chemistry Source Type: research

Benzilydene and thiourea derivatives as new classes of carbonic anhydrase inhibitors: an in vitro and molecular docking study
AbstractCarbonic anhydrase-II (CA-II) catalyzes reversible hydration of carbon dioxide leading to the formation of bicarbonate and a proton. CA-II inhibitors act as biomarkers and therapeutic targets for various diseases such as epilepsy, glaucoma, leukemia, and cystic fibrosis. In the present work, a number of thiourea and benzylidene derivatives were evaluated as CA-II inhibitors. For this, detection of CA-II inhibition was tested through high throughput biochemical mechanism-based assay. Results indicated that thiourea derivatives exhibit remarkable inhibition activity with IC50 values ranging from 1.90  ±...
Source: Medicinal Chemistry Research - November 17, 2020 Category: Chemistry Source Type: research

Design, synthesis, and evaluation of different scaffold derivatives against NS2B-NS3 protease of dengue virus
AbstractThe number of deaths or critical health issues is a threat in the infection caused by Dengue virus, which complicates the situation, as only symptomatic treatment is the current solution. In this regard we have targeted the dengue protease NS2B-NS3 that is responsible for the replication. The series was designed with the help of molecular modeling approach using docking protocols. The series comprised of different scaffolds viz. cinnamic acid analogs (CA1 –CA11), chalcone (C1–C10) and their molecular hybrids (Lik1–Lik10), analogs of benzimidazole (BZ1-BZ5), mercaptobenzimidazole (BS1-BS4), and phe...
Source: Medicinal Chemistry Research - November 17, 2020 Category: Chemistry Source Type: research

Potent antiproliferative active agents: novel bis Schiff bases and bis spiro β-lactams bearing isatin tethered with butylene and phenylene as spacer and DNA/BSA binding behavior as well as studying molecular docking
AbstractA [2+2]-cycloaddition of bis-isatin Schiff bases5a –b and7 with activated aryloxyacetic acid derivatives8a –d afforded bis-spiroisatino β-lactams with aliphatic and aromatic spacers. The structures of the synthesized 2-oxindoles and spirooxindoles were determined based on Fourier-transform infrared spectroscopy, proton-1 and carbon-13 nuclear magnetic resonance spectroscopies and CHN analysis. Our interest in these bis-Schiff bases and bis-spiroisatino β-lactams is for their potential anticancer capabilities. In vitro bioactivity testing against the cervical adenocarcinoma (HeLa) and breast ca...
Source: Medicinal Chemistry Research - November 11, 2020 Category: Chemistry Source Type: research

Novel approach of multi-targeted thiazoles and thiazolidenes toward anti-inflammatory and anticancer therapy —dual inhibition of COX-2 and 5-LOX enzymes
AbstractIt is well established that cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) play a vital role in the initiation and progression of inflammatory reactions. Hence, thiazole and thiazolidene-based pharmacophore molecules were synthesized to obtain dual COX-2 and 5-LOX inhibitory activity. The synthesis of target compounds has been achieved by a novel green strategy. In vitro COX-1, COX-2, and 5-LOX evaluation of these molecules have shown the potential for an improved anti-inflammatory profile. Most promising compound among the series (2-(diphenylamino)-4-(4-nitrophenyl)thiazol-5-yl)(naphthalen-1-yl)methanone7h (I...
Source: Medicinal Chemistry Research - November 1, 2020 Category: Chemistry Source Type: research

Synthesis of pyrazinamide analogues and their antitubercular bioactivity
AbstractThe Yamaguchi reaction is widely and generally applied to synthesize esters and lactones. It involves 2,4,6-trichlorobenzoyl chloride as the Yamaguchi reagent, 4-dimethylaminopyridine, and triethylamine. Pyrazinamide is a crucial first-line drug for tuberculosis treatment, therefore their analogues are interesting in organic synthesis. In general, the synthesis pyrazinamide analogues involve reaction of pyrazine-2-carboxylic acids with thionyl chloride to yield the corresponding acyl chlorides, which on treatment with amines gave pyrazine-2-carboxamides. However, thionyl chloride is listed under the Chemical Weapon...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

A convenient synthesis, reactions and biological evaluation of novel pyrazolo[3,4- b ]selenolo[3,2- e ]pyrazine heterocycles as potential anticancer and antimicrobial agents
AbstractA novel series of 5-amino-6-substituted-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]pyrazines (3a –e) was synthesized by the reaction of the chloro pyrazolo[3,4-b]pyrazine carbonitrile1 with selenium element in the presence of sodium borohydride and ethanol, followed by the reaction with α-halo alkylating agents to produce the selanyl-alkylated derivatives2a –e. The latter compounds underwentThorpe-Ziegler cyclization upon heating with ethanolic sodium ethoxide solution to afford the target selenolopyrazolopyrazine compounds. The 5-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]selenolo[3,2-e]py...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Organotin (IV) complexes from Schiff bases ligands based on 2-amino-3-hydroxypyridine: synthesis, characterization, and cytotoxicity
AbstractA multicomponent reaction was used as a synthetic strategy to prepare organotin (IV) complexes, 2-amino-3-hydroxypyridine, saliciladehydes 5-R-substituted (H, CH3, OCH3, C(CH)3, F, Cl, Br, I, NO2), and dibutyltin(IV) oxide were used as starting materials. The complexes were analyzed by IR, UV –Visible, MS, NMR of1H,13C,119Sn. The complex3a was structurally identified by X-ray crystallography, which revealed a dimeric arrangement where the tin atom possess a distorted hexacoordinated environment in which the deprotonated phenolic oxygen atoms and the nitrogen atom of the azomethine from the ligand are coordina...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Phytochemistry, pharmacology and medicinal uses of Cola (Malvaceae) family: a review
AbstractCola belongs to the family Malvaceae and contains 125Cola plants. Among theCola species,Cola acuminata andCola nitida are the most studied for their pharmacology effects.Cola contains phytochemicals such as alkaloids, caffeine, theobromine, theophylline, quinic acid, chlorogenic acid, purine, ( −)-epicatechin, (+)-catechin, sterols, anthraquinones, flavonoid glycosides, cardenolides, tannins, rostratanic acid, bauerenol, lupeol, acotatarone A, lignoceric acid, betulinic acid, friedelanone, friedelan, stigmasterol, and nonanedioc acid, among others. These secondary metabolites are respons ible for the various ...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Synthesis, biological evaluation and molecular docking studies of Combretastatin A-4 phosphoramidates as novel anticancer prodrugs
AbstractA new series of CA4P analogs (5a-g, 6a-g) has been designed and effectively synthesized via a one-pot reaction from Combretastatin A-4/Erianin, commercially available amino acid esters and phenyl dichlorophosphate. To establish new candidates with anticancer activity, the in vitro antiproliferative effect of these compounds was measured by the CCK8 method on different cancer cell lines such as human liver caricinoma (HepG2), cervical cancer (HeLa) and colorectal carcinoma (HCT-116). The structure-activity relationships between CA4P outgrowth-promoting activity and its analogs suggested that the biaryl structure lin...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

New Pt(II) complexes with 3 ’ -methyl tetrahydro-4 H -thiopyranspiro-5 ’ -hydantoin: synthesis, theoretical and cytotoxic investigation
AbstractThree new platinum complexes with chemical formulascis-[PtL2Cl2],cis-[PtL2I2] andcis-[PtL(NH3)Cl2], whereL is 3’-methyl-4-thio-1H-tetrahydropyranspiro-5’-hydantoin were synthesized and studied. The spectral and theoretical investigations proved that ligand coordinates through sulfur atom from tetrahydrothiopyrane fragment by monodentate manner with platinum ion. The newly synthesized compounds were tested for cytotoxic activity in vitro against four human tumor cell lines using MTT dye-reduction assay for cell viability. The tested compounds displayed cytotoxic effects in a concentration-dependent manne...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Design, synthesis and biological evaluation of novel 1,5-disubstituted isatin derivatives as antitumor agents
AbstractIsatin (1H-indole-2,3-dione) was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. Here, we described the synthesis of a novel series of 1,5-disubstituted isatin derivatives with 2-indolinone scaffold as antitumor agents. Most of the synthesized compounds revealed potent antiproliferative effects in mantle cell lymphoma (MCL) cell lines, among which7l possessed promising activities with IC50 values ranging from 0.4 to 1.3  μM. Following flow cytometric analysis, compound7l efficiently arrested the cell cycle at G2/M phase, ...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Novel amide analogues of quinazoline carboxylate display selective antiproliferative activity and potent EGFR inhibition
AbstractIn the present study, a novel series of quinazoline derivatives is developed for cancer therapy. All the synthesised analogues were evaluated against a panel of 60 human cancer cell lines for the antiproliferative activity. Significant and selective growth inhibition of several solid tumour cell lines such as NCI-H322M, NCI-H522 (non-small cell lung cancer), IGROV1, SK-OV-3 (ovarian cancer), TK-10 (renal cancer) and MDA-MB-468 (breast cancer) was observed. Further, all the new amide analogues strongly inhibited EGFR in low nanomolar range with morpholino quinazoline10 producing activity (IC50 = 6.12&t...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Antifungal activity of aminoalcohols and diamines against dermatophytes and yeast
AbstractDermatomycoses are infections caused by fungi and yeasts and the drug treatment is considered expensive and extensive. Researchers are synthesizing new organic compounds in order to obtain more effective molecules that provide reduced adverse effects. Our research group has synthesized and evaluated the biological activities of aminoalcohol and diamine derivatives, which were considered active against human pathogenic fungi. Therefore, the objective of this study was to evaluate the in vitro antifungal activity of aminoalcohols and diamine derivatives against fungi and yeasts that cause dermatomycoses. The minimum ...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Functionalized imidazolium-based ionic liquids: biological activity evaluation, toxicity screening, spectroscopic, and molecular docking studies
AbstractA series of long-chain imidazolium-based ionic liquids (ILs) 1-dodecyl-3-methylimidazolium chloride (1), 1,3-bis(octyloxycarbonylmethyl)imidazolium chloride (2) and 1-dodecyloxycarbonylmethyl-3-methyloxycarbonylmethylimidazolium chloride (3), were synthesized and evaluated as antimicrobials against a wide range of bacteria and fungi. Toxicological risks of selected compounds were assessed using the biomodels of various organizational and functional levels. All compounds demonstrated significant antibacterial and antifungal activity. The toxicity results indicate that ILs containing an ester functional group in the ...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

Triphenylphosphonium conjugates of 1,2,3-triazolyl nucleoside analogues. Synthesis and cytotoxicity evaluation
AbstractA series of triphenylphosphonium (TPP) conjugates of 1,2,3-triazolyl analogues of several pyrimidine nucleosides was synthesized and evaluated for the in vitro cytotoxicity against human cancer cell lines M-HeLa, MCF-7, PANC-1, PC-3, DU145, SKOV-3, A275, and normal human cell line WI-38. In these TPP-conjugates triphenylphosphonium cation was attached via a tetramethylene chain to theN-3 atom of the heterocycle moiety (uracil, thymine, quinazoline-2,4-dione), which was coupled with the D-ribofuranosyl-1,2,3-triazol-4-yl fragmentvia methylene or tetramethylene linker. It was shown for the first time that the conjuga...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

NF- κB regulation by bisbenzylisoquinoline alkaloids in human T cells: a structure–activity relationship study
AbstractSuppressive potencies of tetrandrine, isotetrandrine, fangchinoline, berbamine, dauricine, cepharanthine, and armepavine on expression and activation of NF- κB in MOLT-4 cells, MOLT-4/DNR cells, peripheral blood mononuclear cells (PBMCs) of healthy subjects and PBMCs of dialysis patients were compared. In MOLT-4 cells, the suppressive potencies evaluated by the IC50 values were isotetrandrine  >  cepharanthine >  tetrandrine >  dauricine >  fangchinoline >  berbamine or armepavine. In MOLT-4/DNR cells, the order was isotetran...
Source: Medicinal Chemistry Research - October 7, 2020 Category: Chemistry Source Type: research

First in class ( S , E )-11-[2-(arylmethylene)hydrazono]-PBD analogs as selective CB2 modulators targeting neurodegenerative disorders
AbstractNewly designed pyrrolo[2,1-c][1,4]benzodiazepines tricyclic skeleton has shown potential clusters of cannabinoid receptors CB1/CB2 selective ligands. CB2 plays a critical role in microglial-derived neuroinflammation, where it modulates cell proliferation, migration, and differentiation into M1 or M2 phenotypes. Beginning with computer-based docking studies accounting the recently discovered X-ray crystal structure of CB2, we designed a series of PBD analogs as potential ligands of CB2 and tested their binding affinities. Interestingly, computational studies and theoretical binding affinities of several selected (S,...
Source: Medicinal Chemistry Research - October 3, 2020 Category: Chemistry Source Type: research

Synthesis of novel selenotetrazole purine derivatives and their potential chemotherapeutic activities
In this study, a series of novel artificial purine nucleosides bearing selenotetrazole pharmacophore,4a–4h, were synthesized. In order to get preliminary information about their cytotoxic activities, the interaction of compounds with DNA was investigated by UV titration and agarose gel electrophoresis and transcription inhibition studies were performed. The cytotoxic effects of the compounds against B16 melanoma, OV90 ovarian cancer, JM1 lymphoma cell lines, and PHA-induced peripheral blood lymphocytes were also investigated. In cell assay studies, the effects of the compounds on synthesis and mitosis stage of cell c...
Source: Medicinal Chemistry Research - October 1, 2020 Category: Chemistry Source Type: research

Identification of potential anti-inflammatory and melanoma cytotoxic compounds from Aegiceras corniculatum
AbstractMany chemicals found in mangroves reportedly exhibit potent anticancer, antibacterial, anti-inflammatory, antioxidant, and antitumor properties. Several of such compounds include feature unique structures and display interesting pharmacological effects. Few medicinal mangrove plants from Vietnam have been characterized with regard to their chemical constituents.Aegiceras corniculatum (L.) Blanco is a mangrove shrub that exhibits activity against various types of cancer. To identify new secondary metabolites and determine the source(s) of biological activity in Vietnamese medicinal mangrove plants, the chemical cons...
Source: Medicinal Chemistry Research - September 16, 2020 Category: Chemistry Source Type: research

Aryl-enclosed polyketides from mangrove sediment associated bacterium Bacillus amyloliquefaciens attenuating pro-inflammatory 5-lipoxygenase
AbstractTwo aryl-enclosed polyketides were identified from the ethyl acetate extract of mangrove sediment associated bacteriumBacillus amyloliquefaciens, and were characterized as 1-(8-hydroxy-1-oxoisochroman-3-yl)propyl 4 ′-(6′-hydroxy-8′-oxotetrahydrofuran-5′-yl)acetate (compound1) and 6 ′a-(3′-(1′-(8-hydroxy-1-oxoisochroman-3-yl)propoxy)-3′-oxoethyl)-8′-oxotetrahydrofuran-6′-yl butyrate (compound2) by detailed spectroscopic techniques encompassing two-dimensional nuclear magnetic resonance and mass spectroscopic experiments. Polyketide compound2 bearing oxotetr...
Source: Medicinal Chemistry Research - September 16, 2020 Category: Chemistry Source Type: research

Radiosynthesis of [ 11 C]EI1 for imaging EZH2 using positron emission tomography
AbstractEnhancer of zeste homolog 2 (EZH2) is responsible for the methylation of lysine 27 of histone H3 (H3K27) leading to transcriptional repression. Consequently, EZH2 is related with several diseases including cancers, as overexpressed EZH2 can down-regulate cancer suppressor genes. Therefore, EZH2 became a promising target for cancer treatment and diagnosis and in vivo imaging of EZH2 is critical for diagnosis and treatment monitor. In the present work, we radiolabeled a specific inhibitor of EZH2, [11C]EI1, investigated its pharmacokinetics and performed micro PET/CT imaging. Results showed that the half-life of the ...
Source: Medicinal Chemistry Research - September 13, 2020 Category: Chemistry Source Type: research

Thiosemicarbazone and thiazole: in vitro evaluation of leishmanicidal and ultrastructural activity on Leishmania infantum
AbstractLeishmaniasis is a much-neglected tropical disease, especially in developing countries. Visceral Leishmaniasis (VL) is the most severe form of this infection caused byLeishmania infantum specie. It affects the splenic and hepatic systems and, when left untreated, it is fatal in 95% of cases. There is no human vaccine available and the recommended treatment not only presents adverse effects but it enables the development of resistant strains if interrupted. Hence, the urgent search for new leishmanicidal compounds. In the present work, we evaluated the in vitro leishmanicidal action of new thiosemicarbazone and thia...
Source: Medicinal Chemistry Research - September 9, 2020 Category: Chemistry Source Type: research

In vitro dual-target activities and in vivo antidiabetic effect of 3-hydroxy- N -( p -hydroxy-phenethyl) phthalimide in high-fat diet and streptozotocin-induced diabetic golden hamsters
AbstractThe 3-hydroxy-N-(p-hydroxy-phenethyl) phthalimide (HNHP), which showed in vitro peroxisome proliferator-activated receptor- γ (PPAR-γ) activation and in vivo anti-inflammatory effect in our previous study, was speculated to be a dual-target lead compound because similar structures exhibited α-glucosidase inhibitory activities. To investigate the dual targeting potential, molecular docking of HNHP was performed targeti ng on PPAR-γ and α-glucosidase, and HNHP was found to bind with dual targets in the known active sites with relatively high affinities. The in vitro α-glucosidase i...
Source: Medicinal Chemistry Research - September 9, 2020 Category: Chemistry Source Type: research

Anti-inflammatory polyoxygenated furanocembranoids, salmacembranes A –B from the sea urchin Salmacis bicolor attenuate pro-inflammatory cyclooxygenases and lipoxygenase
AbstractTwo undescribed polyoxygenated furanocembranoid derivatives, methyl 15-(9-hydroxy-8-methoxy-2,12-dimethyl-15-oxa-bicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-3-yl)propanoate (salmacembrane A) and 1-(16-methyl-2,16-dihydrofuran)-8-methoxy-12-methyl-20-oxabicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-9-ol (salmacembrane B), were isolated from the organic extract of sea urchinSalmacis bicolor (family Temnopleuridae) by extensive chromatographic purification. Their structures were elucidated using detailed spectroscopic evidence. Salmacembrane A displayed significantly greater attenuation property against pro-inflammatory cyc...
Source: Medicinal Chemistry Research - September 9, 2020 Category: Chemistry Source Type: research

What are the drugs having potential against COVID-19?
AbstractA disease emerged in the city of Wuhan, Hubei Province, Central China in the last month of 2019. It was pneumonia caused by a newly emerged coronavirus called COVID-19, later. Coronaviruses are enveloped RNA viruses belong to the Betacoronavirus family and infected birds, humans, and other mammals. In March 2020, the World Health Organization declared the COVID-19 outbreak could be characterized as a global pandemic because the disease spread, and a large number of people were infected and died in many countries on different continents by virtue of this new virus. Now, intensive work is underway about the pathogeni...
Source: Medicinal Chemistry Research - September 9, 2020 Category: Chemistry Source Type: research

Quercetin and cervical cancer: a view of great scope
AbstractCervical cancer (CC) is the most common gynecological cancer and is one of the results of high-risk HPV infection. Recent statistics demonstrate that 90% of cervical cancer cases are diagnosed in low- and middle-income countries. These results are observed due to the poor sanitation and lack of proper preventive strategies. Quercetin is a plant compound with a great number of beneficial properties which increasing the level of sanitation or acting as a preventive agent are not of its capabilities; however, what quercetin is capable of is preventing the cancer from progression in CC patients. Cell proliferation, gro...
Source: Medicinal Chemistry Research - September 9, 2020 Category: Chemistry Source Type: research

Antioxidant enzyme regulating and intracellular ROS scavenging capacities of two novel bioactive peptides from white grub larvae ( Polyphylla adstpersa ) hydrolysate in A549 cells
In conclusion, our results suggest that YK-10 and LP-10 peptides from WGLH have antioxidant activities and can protect A549 cells against free radicals ’ damages. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - September 7, 2020 Category: Chemistry Source Type: research

Synthesis, molecular docking and ADME prediction of some new benzimidazole carboxamidines derivatives as antimicrobial agents
In this study, 15 new 1H-benzimidazole-5-carboxamidine derivative compounds that could be new antimicrobial agents were synthesized and their antimicrobial activities were determined using the microdilution method. When the activity results were examined, it was observed that the antibacterial effects of the new benzimidazole derivatives were weaker than standard drugs, but some derivatives showed significant efficacy against MRSA and VREF with the value of MIC: 8  µg/ml compared to reference drugs. The antifungal effects of the compounds were found to be weaker compared to the reference drugs. Molecular docki...
Source: Medicinal Chemistry Research - September 4, 2020 Category: Chemistry Source Type: research

Genomics insights of SARS-CoV-2 (COVID-19) into target-based drug discovery
AbstractCoronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is a global health emergency and no clinically approved vaccines or antiviral drugs available to date. Intensive research on SARS-CoV-2 is urgently warranted to understand its pathogenesis and virulence mechanisms and to discover target-based antiviral therapeutics. Among various research logics, current bioinformatics highlights novel testable hypotheses for systematic drug repositioning and designing against COVID-19. A total of 121 articles related to bioinformatics facets of this virus wer...
Source: Medicinal Chemistry Research - August 29, 2020 Category: Chemistry Source Type: research

Design, synthesis, and biological evaluation of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives as anticancer agents
AbstractA novel series of 1-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-3-phenylurea derivatives (5a –l) were designed and synthesized as sorafenib analogs. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, HepG2, A549, and HeLa cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells. In particular, 2-F, 4-Cl, and 2,6-diF substituted derivatives (5d,5g, and5k) showed promising activities, especially against Hela cancer cells (IC50 = 0.37, 0.73 and 0....
Source: Medicinal Chemistry Research - August 23, 2020 Category: Chemistry Source Type: research

Antioxidant, antiproliferative, and acetylcholinesterase inhibition activity of amino alcohol derivatives from 1,4-naphthoquinone
AbstractNatural and synthetic naphthoquinones have demonstrated numerous biological activities; therefore, they provide an interesting scaffold for medicinal chemists in the search for new drugs. A series of amino alcohol derivatives from 1,4-naphthoquinone with a free (2a–e) and acetylated (3a–d) hydroxyl group were synthesized, characterized, and evaluated as antioxidant agents employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2 ′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compoun...
Source: Medicinal Chemistry Research - August 23, 2020 Category: Chemistry Source Type: research

Polyether macrocyclic polyketide from the muricid gastropod Chicoreus ramosus attenuates pro-inflammatory 5-lipoxygenase
AbstractMacrocyclic compounds of multifaceted structural scaffolds are being increasingly reported from the marine environment, and gaining commercial importance due to their ability to inhibit the pro-inflammatory mediators. An unreported polyether macrocyclic polyketide characterized as 6-(butoxy)-13,15,22-trihydroxy-3,18-dioxatricyclo[18.3.1.011,16]tricosa-9,20-diene-4,8-dione was isolated from the marine gastropod molluscChicoreus ramosus (family Muricidae). The compound displayed potential anti-inflammatory property by inhibiting 5-lipoxygenase (IC50 0.42  mg mL−1), which was analogous to the nonst...
Source: Medicinal Chemistry Research - August 21, 2020 Category: Chemistry Source Type: research

Ionophoric polyphenols are permeable to the blood –brain barrier, interact with human serum albumin and Calf Thymus DNA, and inhibit AChE enzymatic activity
AbstractAlzheimer ’s disease (AD) is the most common form of dementia that affects more than 40 million people around the world. The incidence is expected to rapidly increase due to the lack of any effective treatment. In previous work we synthesized a family of five ionophoric polyphenols (compounds1–5) that targeted important aspects related to AD, such as the toxic aggregation of amyloid- β peptides, the production of reactive oxygen species, or the excessive presence of Cu2+ ions. Here, in order to gain insights into their potential therapeutic value, we have tested the ability of compounds1–5 to...
Source: Medicinal Chemistry Research - August 20, 2020 Category: Chemistry Source Type: research

Preparation and α -glucosidase inhibition of andrographolide derivatives
AbstractSeries of novel analogs, which were primarily modified on its lactone moiety, was synthesized based on Andrographolide (1), a natural product sesquiterpene inhibitor ofα-glucosidase. Among new analogs, 14-deoxy-11,12-didehydro-15-(4-ethoxybenzylidene)andrographolide (3h) was determined to have the greatest potential ofα-glucosidase inhibitor through the calculation of IC50 value of 160  ± 5.1 μM, a significant improvement compared to the clinical dose of Acarbose, which showed the IC50 value of 390  ± 8.1 μM. In addition, 14-deoxy-11,12-dideh...
Source: Medicinal Chemistry Research - August 16, 2020 Category: Chemistry Source Type: research

Propargylated monocarbonyl curcumin analogues: synthesis, bioevaluation and molecular docking study
AbstractIn the current experimental study, we have synthesised new monocarbonyl curcumin analogues bearing propargyl ether moiety in their structure and evaluated for in vitro antifungal and radical scavenging activity. The antifungal activity was carried out against five human pathogenic fungal strains such asCandida albicans,Fusarium oxysporum,Aspergillus flavus,Aspergillus niger andCryptococcus neoformans. Most of the curcumin analogues displayed excellent to moderate fungicidal activity when compared with standard drug Miconazole. Also, synthesised analogues exhibited potential radical scavenging activity as compared w...
Source: Medicinal Chemistry Research - August 9, 2020 Category: Chemistry Source Type: research

A review of antimalarial activity of two or three nitrogen atoms containing heterocyclic compounds
AbstractMalaria, a nocuous disease, which has become a major challenge for the health resulting in deaths of millions of people around the globe. Malaria is a parasitic disease propagated by mosquitoes and infects the human beings. Several species ofPlasmodium are responsible for this life-threatening disease andPlasmodium falciparum being the most virulent. In order to eradicate the malarial parasite, the researchers are making consistent efforts in synthesizing new antimalarial drug candidates by paying attention to the various drug targets. In this manuscript, the main focus is on the antimalarial activity of numerous h...
Source: Medicinal Chemistry Research - August 6, 2020 Category: Chemistry Source Type: research

Design, synthesis and in silico evaluation of benzoxazepino(7,6-b)quinolines as potential antidiabetic agents
AbstractThe second-generation XPhos palladium preformed catalyst-based C –N cross-coupling through Buchwald–Hartwig amination with primary and secondary amines towards functionalized benzoxazepino(7,6-b)quinolines is accounted for. The microwave irradiation in dioxane provided the desired highly functionalized oxazepino quinolines,5, in high yield and purity from the corresponding 2-chloro-3-formyl quinolines,1, via intermediate,4, in a sequential cyclization/Buchwald amination strategy. Besides, functional group tolerance, low catalyst loading, microwave assistance, and a wide scope of reactions are the advant...
Source: Medicinal Chemistry Research - August 4, 2020 Category: Chemistry Source Type: research

Biological activities of [1,2,4]triazolo[1,5- a ]pyrimidines and analogs
AbstractThe [1,2,4]triazolo[1,5-a]pyrimidines (TPs) comprise an important class of non-naturally occurring small molecules that aroused the interest of researches. This scaffold is present in diverse important structures in agriculture and medicinal chemistry, such as antibacterial, antifungal, antiviral, antiparasitic, and anticancer. As over the decades the development of the chemistry and application of 1,2,4-triazolo[1,5-a]pyrimidines has continued and even accelerated, in this review, we thoroughly discussed the applications of TPs in both agriculture and medicinal chemistry highlighting the significance of this nucle...
Source: Medicinal Chemistry Research - August 1, 2020 Category: Chemistry Source Type: research

Anti-urease and cytotoxic activity of 1-Nitro-2-phenylethane and Nerolidol; two major compounds isolated from the seeds of Dennettia tripetala
AbstractThe study investigated the anti-urease and cytotoxic activities of two major essential oil compounds; 1-Nitro-2-phenylehtane (NPE) and Nerolidol, isolated from the acetone extract ofDennettia tripetala (Pepper Fruit) seeds. Structural characterization of these compounds was performed by NMR, E1MS, and FT-IR spectroscopic techniques. Anti-urease activity of the compounds on Jack bean Urease was accessed by the indophenol method; molecular docking analysis using MOE 2015.010 program was performed to explain the possible mechanism of interaction between the compounds and urease enzyme. Cytotoxic activities of the comp...
Source: Medicinal Chemistry Research - August 1, 2020 Category: Chemistry Source Type: research