Drug –protein adducts: past, present, and future
AbstractResearch over the past half-century has demonstrated that the metabolism of drugs and other foreign compounds to chemically reactive intermediates that bind covalently to endogenous proteins can, in certain cases, lead to organ damage or to immune-mediated adverse reactions. While the chemistry of metabolic activation is now relatively well understood, the molecular events that link exposure to reactive metabolites to toxic sequalae remain ill-defined. In particular, the role of covalent protein binding in drug-induced toxicities is unclear, and has been a controversial issue in drug discovery efforts. In this arti...
Source: Medicinal Chemistry Research - May 27, 2020 Category: Chemistry Source Type: research

Template-based alignment modeling: an innovative ligand-based approach for medicinal chemists
AbstractA single protein-binding pocket often times binds to a diverse range of ligands with distinct structural features. Understanding the structural correlations of the different ligands remains a major challenge in medicinal chemistry research. We recently developed the template-based alignment modeling (TAM) method as a simple yet effective approach for understanding structure –activity relationships (SARs) for a variety of medicinal agents. In this article, we briefly review the developmental process of TAM, and then showcase some potential applications. Finally, within the conceptual framework of TAM, we discu...
Source: Medicinal Chemistry Research - May 27, 2020 Category: Chemistry Source Type: research

Bergaptol, a mechanism-based inactivation of CYP2C9
In this study, BGT was found to induce time-, concentration-, and NADPH-dependent irreversible inhibition of CYP2C9. A GSH co njugate was detected in an incubation mixture containing CYP2C9, BGT, NADPH, and GSH. Further mechanistic investigation revealed that a γ-ketoenal metabolite was responsible for the enzyme inactivation. The obtained data indicate that BGT was a mechanism-based inactivator of CYP2C9. The study would facilitate the understanding of the mechanistic insight into fruit–drug interactions mediated by grapefruits. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - May 26, 2020 Category: Chemistry Source Type: research

Discovery of anti-influenza nucleoside triphosphates targeting the catalytic site of A/PR/8/34/H1N1 polymerase
AbstractIn an effort to develop potent anti-influenza drugs that inhibit the activity of influenza virus RNA-dependent RNA polymerase (IAV RdRp), a database of nucleoside triphosphates with ~800 molecules were docked with the homology model of IAV RdRp from A/PR/8/34/H1N1 strain. Out of top 12 molecules that bind with higher affinities to the catalytic site of IAV RdRp above and below the PB1 priming loop, only seven molecules decreased the transcriptional activity of the viral RNA polymerase with an IC50 in the range of 0.09 –3.58 µM. Molecular docking combining with experimental study indicated that th...
Source: Medicinal Chemistry Research - May 24, 2020 Category: Chemistry Source Type: research

A comprehensive review of ethnopharmacological uses, phytochemistry, biological activities, and future prospects of Nigella glandulifera
AbstractNigella glandulifera Freyn et Sint (N. glandulifera) is frequently added tonaan (a kind of crusty pancake and a favorite food of the Uyghur and Kazak people) as a spice. The water decoction ofN. glandulifera was used as traditional Uighur medicine to treat tinnitus, amnesia, amenorrhea, hypogalactia, heat stranguria, urethral calculus, alopecia and hair-blacking, edema, and bronchial asthma. This review aimed to give an updated, comprehensive summary on the traditional uses, pharmacology, phytochemistry and toxicology ofN. glandulifera to provide some reminders for future research. More than 78 chemical compounds w...
Source: Medicinal Chemistry Research - May 22, 2020 Category: Chemistry Source Type: research

Synthesis and biological evaluation of selected 7-azaindole derivatives as CDK9/Cyclin T and Haspin inhibitors
AbstractThe 7-azaindole scaffold attracts attention due to its value in the design of inhibitors of diseases related protein kinases. However, this scaffold has not been evaluated against Haploid germ cell-specific nuclear protein kinase (Haspin). Herein, we report the synthesis of a select set of 7-azaindole derivatives and their evaluation against Haspin. The compounds were also evaluated against CDK9/Cyclin T kinase. The synthesis of 7-azaindole derivatives was achieved through Suzuki coupling using appropriate halogenated 7-azaindole and boronic acids. Seven of the screened compounds exhibited activity as CDK9/Cyclin T...
Source: Medicinal Chemistry Research - May 22, 2020 Category: Chemistry Source Type: research

Synthesis and evaluation of substituted phenyl cycloalkylureas and bioisosteres as IL-6 expression inhibitors
AbstractInflammation is an important, normal, and complex host defense response to injury, autoimmune responses or infectious agents. However, chronic inflammation is associated with diseases like rheumatoid arthritis, cancers, cardiovascular diseases, diabetes, and obesity, and over 60% of deaths worldwide. Interleukine-6 is one of the key proinflammatory cytokines involved in inflammation processes and therefore considered as a valuable drug target. We have prepared three series of new drugs referred to as substituted phenyl cycloalkylureas (PcAUs), phenyl cycloalkylthioureas (PcATUs) and phenyl cycloalkylsquaramides (Pc...
Source: Medicinal Chemistry Research - May 19, 2020 Category: Chemistry Source Type: research

Design, synthesis, and biological evaluation of novel benzo[b]thiophene-diaryl urea derivatives as potential anticancer agents
AbstractA hybrid pharmacophore approach was applied to design and synthesize a series of benzo[b]thiophene-diaryl urea derivatives17a –g with potential anticancer effect. In vitro antiproliferative activities of all target compounds were evaluated against HT-29 and A549 cancer cell lines. Three compounds17b,17d, and17f exhibited antiproliferative activities on both cell lines comparable to that of the positive reference drug sorafenib. Notably, compound17d demonstrated the highest activity with IC50 values of 5.91 and 14.64  μM on HT-29 and A549 cells, respectively. It also induced apoptosis and cell cycle ...
Source: Medicinal Chemistry Research - May 19, 2020 Category: Chemistry Source Type: research

Synthesis and biological evaluation of a new series of 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as new anticancer agents
AbstractThe diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Most of the target compounds demonstrate significant antiproliferative effects on all the selective cancer cell lines. The calculated IC50 values were reported. The target compound 1-(4-chlor...
Source: Medicinal Chemistry Research - May 18, 2020 Category: Chemistry Source Type: research

N -arylated oxathiazinane heterocycles are convenient synthons for 1,3-amino ethers and 1,3-amino thioethers
AbstractThis communication describes a variety of nucleophilic ring openings ofN-arylated oxathiazinane heterocycles. We find that this reaction is compatible with phenoxides, naphthoxides, and thiolates and allows for the rapid assembly ofN-aryl-amino ethers andN-aryl-amino thioethers. Fourteen examples are shown and a mechanistic pathway is hypothesized. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - May 17, 2020 Category: Chemistry Source Type: research

Synthesis and in vitro antimycobacterial and antileishmanial activities of hydroquinone-triazole hybrids
AbstractInfectious diseases such as tuberculosis and leishmaniasis are leading causes of human death. One of the major factors contributing to the poor control of these diseases is primarily the reduced effectiveness of the existing chemotherapies as result of the increasing rise of multidrug-resistant strains of their causative agents. This leads to the imperative need to develop new and effective drugs. In search for such agents, a series of hydroquinone-triazole hybrids was investigated. The design, synthesis, and biological activities against the human virulent H37Rv strain ofMycobacterium tuberculosis (Mtb) andLeishma...
Source: Medicinal Chemistry Research - May 12, 2020 Category: Chemistry Source Type: research

Synthesis of 1-(4-hydroxy-3-methoxyphenyl)-2,3,4,9-tetrahydro-1H- β-carboline-3-carboxylic acid derivatives as mast cell stabilizers
AbstractThe role of mast cells can be protective or harmful; depending upon the physiological/pathological condition in which they get activated. The latter role is due to mast cell degranulation and release of an array of incendiary mediators. Mast cells have a well-established role in diseases like allergy, eczema, anaphylactic shock, mastocytosis, and other miscellaneous mast cell diseases. Previously, we have shown that spiro- β-carboline alkylated analogs have mast cells stabilization activity. Recently, tryptophan has been reported to suppress the mast cell activation. Indeed, vanillin analogs were reported to i...
Source: Medicinal Chemistry Research - May 12, 2020 Category: Chemistry Source Type: research

Synthesis and biological evaluation of novel N -2,4-dimethoxyphenyl dithiolopyrrolone derivatives as bacterial RNA polymerase inhibitors
AbstractEighteen novelN-2,4-dimethoxyphenyl dithiolopyrrolone derivatives inhibiting bacterial RNA polymerase (RNAP) were synthesized based on dithiolopyrrolone scaffold. Some compounds displayed potent antimicrobial activity against Gram-positive bacteria ofStaphylococcus aureus andStreptococcus pneumoniae, but not the Gram-negative bacteria ofEscherichia coli andPseudomonas aeruginosa. Moreover, the most promising compound7b showed potent antibacterial activity against clinical isolates of MRSA, VRSA, RRSA, and MPRSP with MIC values in the range of 0.125 –2 μg/mL, and potent inhibitory activity againstEsc...
Source: Medicinal Chemistry Research - May 12, 2020 Category: Chemistry Source Type: research

Cytotoxicity, anticancer, and antioxidant properties of mono and bis-naphthalimido β-lactam conjugates
This article reports the diastereoselective synthesis of some novel naphthalimido and bis-naphthalimido β-lactam derivatives and a preliminary evaluation of their anticancer properties. The reactions were completely diastereoselective, leading exclusively to the formation ofcis- β-lactams11a –l andtrans-bis- β-lactams16a –g. All of these compounds were obtained in good to excellent yields and their structures were established based on IR,1H NMR,13C NMR spectral data, and elemental analysis. Each of the β-lactams was screened for antioxidant and anticancer activities. Our results showed that ...
Source: Medicinal Chemistry Research - May 10, 2020 Category: Chemistry Source Type: research

Synthesis and antitumor activity of novel gibberellin derivatives with tetracyclic diterpenoid skeletons
AbstractGibberellic acid (GA3) is a tetracyclic diterpene compound which displays interesting bioactivities. Recently, its potential use for preparing antitumor drug leads has been highlighted, and various modification methods of GA3 have been reported. Aiming at investigating GA3 derivatives with potential antitumor activities, ring distortion of GA3 under different conditions was carried out, and this was followed with amidation or substitution, yielding four series of derivatives. The chemical structure of these compounds were analyzed by1H-NMR,13C-NMR, HRMS, FTIR and polarimetry, and SXRD was employed to further confir...
Source: Medicinal Chemistry Research - May 9, 2020 Category: Chemistry Source Type: research

Synthesis and biological evaluation of α- and β-hydroxy substituted amino acid derivatives as potential mGAT1–4 inhibitors
In this study, we report the synthesis and biological evaluation of a variety of α- and β-hydroxy substituted amino acid derivatives as potential amino acid subunits in inhibitors of GABA uptake transporters (GATs). In order to ensure that the test compounds adopt a binding pose similar to that presumed for related larger GAT inhibitors, lipophilic residues were introduced eit her at the amino nitrogen atom or at the alcohol function. Several of the synthesized compounds were found to exhibit similar inhibitory activity at the GAT subtypes mGAT2, mGAT3, and mGAT4, respectively, as compared with the reference N-b...
Source: Medicinal Chemistry Research - May 8, 2020 Category: Chemistry Source Type: research

3D-QSAR, HQSAR, molecular docking, and new compound design study of 1,3,6-trisubstituted 1,4-diazepan-7-ones as human KLK7 inhibitors
In this study, the structure and activity relationship of 40 human KLK7 inhibitors was explored by three-dimensional quantitative structure –activity relationship (3D-QSAR) and hologram quantitative structure–activity relationship (HQSAR). 3D-QSAR including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis fields (CoMSIA), and Topomer comparative molecular field analysis (Topomer CoMFA). From the data we got, the 3D-QSAR models (CoMFA withq2 = 0.755,r2 = 0.994; CoMSIA withq2 = 0.602,r2 = 0.980; Topomer CoMFA wi...
Source: Medicinal Chemistry Research - May 5, 2020 Category: Chemistry Source Type: research

Antibacterial and antibiofilm activities of synthetic analogs of 3-alkylpyridine marine alkaloids
AbstractNowadays, the emergence of superbugs is one of the most serious public health problems. Strains ofStaphylococcus aureus andKlebsiella pneumoniae, resistant to many antimicrobials available in clinical practice, have become increasingly common. The development of new drugs for the treatment of infections caused by these pathogens is necessary and urgent. A series of 11 analogs of marine 3-alkylpyridine alkaloids was evaluated in vitro for its antibacterial potential. Compound6, a synthetic analog of viscosaline, exhibited significant activity againstS. aureus, including an MRSA strain (MIC  = 2 ...
Source: Medicinal Chemistry Research - May 4, 2020 Category: Chemistry Source Type: research

Oxygenated xanthones as P-glycoprotein modulators at the intestinal barrier: in vitro and docking studies
In conclusion, the in vitro results confirmed OXs potential for P-gp induction and/or activation and suggested SW480 cells as a suitable in vitro model for these studies. However, P-gp activation did not protected SW480 cells against MTX cytotoxicity.In silico studies suggested the different binding locations as a limiting step in the P-gp-mediated efflux of its substrates under P-gp activation. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - April 29, 2020 Category: Chemistry Source Type: research

Microwave-assisted synthesis, molecular docking and anti-HIV activities of some drug-like quinolone derivatives
AbstractIn targeted therapy of breast cancer, human epidermal growth factor receptor 2 HER2 (PDB ID: 3PP0) is being considered as a promising route to design novel anti-breast cancer drugs. In this work, we report two of novelN-substituted pyrrolidine at C-8 position of quinolone derivatives18 and19, their synthesis under microwave technique, spectral methods, molecular docking study and anti-HIV activities. Docking study exhibited hydrogen bonding, polar, and Van der Waals interactions with the active site residues of HER2 target. The binding energy and hydrogen bonding interactions show that synthesized compounds are bei...
Source: Medicinal Chemistry Research - April 29, 2020 Category: Chemistry Source Type: research

Antiproliferative activity of naphthoquinones and indane carboxylic acids from lapachol against a panel of human cancer cell lines
AbstractLapachol (1) is a well-studied natural product isolated from plants of theBignoniaceae family and demonstrates diverse biological effects. Historically, chemical transformation of the lapachol scaffold has yielded new derivatives with impressive biological activity and rich chemical diversity. β-lapachone (2), α-lapachone (3), and 2-acetylfuronaphthoquinone (4) are examples of analogs derived from lapachol that show superior antitumor activity compared with the natural product. In the present study, novel indane carboxylic acid: 2,2-dimethyl-2,3-dihydroindeno[1,2-b]pyran-4,5-dione (9) and methyl 5-hydrox...
Source: Medicinal Chemistry Research - April 29, 2020 Category: Chemistry Source Type: research

Inhibitory activity on cholinesterases produced by aryl-phthalimide derivatives: green synthesis, in silico and in vitro evaluation
ConclusionThe modified version of the Bonting and Featherstone method was successfully adapted to quantify BuChE activity. Dioxoisoindolines C and D displayed greater inhibition of BuChE versus AChE, with good inhibition of both enzymes. Thus, they are promising lead compounds for developing new BuChE/AChE inhibitors. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - April 27, 2020 Category: Chemistry Source Type: research

Synthesis and evaluation of anticancer effect of a novel molecule based-on pillar[5]arene including multi quinoline units
In this study, pillar[5]arene containing ten terminal alkynyl-functional group was prepared and carried out an optimization procedure for target molecule with using 5-hydroxyquinoline molecule known with biological activity. The novel molecule was named as iso-QP[5] and characterized by FT-IR, melting point, NMR, elemental analysis, and mass spectroscopy. The aim was to evaluate the anticancer effects of iso-QP[5] on MCF7 human breast cancer cells. The IC50 dose of iso-QP[5] in MCF7 cells was found to be 25  µM for 24 h using XTT assay. Expressions of eight genes for apoptosis were determined by qPCR. T...
Source: Medicinal Chemistry Research - April 27, 2020 Category: Chemistry Source Type: research

Synthesis and biological screening of a novel enaminone-grafted trithiocarbonate: a potential anticancer and antimicrobial agent
AbstractA need exists to develop safe and efficacious medications to treat major diseases such as cancer and infectious diseases. In response to this need, we synthesized a novel enaminone, which structurally belongs to the trithiocarbonate class engrafted by an enaminone group. The anticancer and antimicrobial activities were evaluated by utilizing three different types of human cancer (MDA-MB-231, LoVo, and HepG2) and a wide field of microbes (G+ and G− bacteria, yeast, and molds). The tested compound3 exhibited moderate growth suppression activity versus all examined human tumor cells, with values of IC50 ranging ...
Source: Medicinal Chemistry Research - April 21, 2020 Category: Chemistry Source Type: research

Synthesis and antimicrobial evaluation of new thiazolyl-1,2,3-triazolyl-alcohol derivatives
AbstractA new series of 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol (6a-t) have been synthesized by a click reaction of 2-azido-1-(4-methyl-2-phenylthiazol-5-yl)ethanone (3a-e) with substituted ethynylbenzene (4a-c) followed by reduction with sodiumboro hydride. The newly synthesized 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol derivatives were screened for in vitro antibacterial activityagainst a Gram negative strains,Escherichia coli (National Collection of Industrial Microorganisms, NCIM 2574), a Gram positive strainStaphylococcus albus (NCIM 2178) and in vitro ...
Source: Medicinal Chemistry Research - April 20, 2020 Category: Chemistry Source Type: research

Multifunctional quinoxaline-hydrazone derivatives with acetylcholinesterase and monoamine oxidases inhibitory activities as potential agents against Alzheimer ’s disease
AbstractMultitarget molecules are considered as an effective way for the treatment of AD, instead of the classic one-drug-one-target strategy because of the multifactorial nature of AD. A variety of studies indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted quinoxaline-hydrazone derivatives were synthesized, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity and MAOA/B inhibitory activity. Based on the experimental results, compound5l exhibite...
Source: Medicinal Chemistry Research - April 19, 2020 Category: Chemistry Source Type: research

Novel allosteric PARP1 inhibitors for the treatment of BRCA-deficient leukemia
AbstractThe successful use of PARP1 inhibitors like olaparib (Loparza ®) in the treatment of BRCA1/2-deficient breast cancer has provided clinical proof-of-concept for applying personalized medicine based on synthetic lethality to the treatment of cancer. Unfortunately, all marketed PARP1 inhibitors act by competing with the cofactor NAD+ and resistance is already developing to this anticancer mechanism. Allosteric PARP1 inhibitors could provide a means of overcoming this resistance. A high throughput screen performed by Tulin et al. identified 5F02 as an allosteric PARP inhibitor that acts by preventing the enzymatic ...
Source: Medicinal Chemistry Research - April 19, 2020 Category: Chemistry Source Type: research

Cytotoxicity of some synthetic bis(arylidene) derivatives of cyclic ketones towards cisplatin-resistant human ovarian carcinoma cells
AbstractSymmetrical α,αʹ-bis(arylidene)ketones were prepared by acid-catalyzed aldol condensations between aliphatic ketones (e.g., cyclopentanone, 4-alkylcyclohexanones, tetrahydropyran-4-one, and tetrahydrothiopyran-4-one) and two equivalents of an aromatic hydroxyaldehyde (e.g., 4-hydroxybenzaldehyde, 3,4-dihydro xybenzaldehyde, vanillin, isovanillin, and 3-fluoro-4-hydroxybenzaldehyde). Most of the compounds were cytotoxic towards the cisplatin-resistant human ovarian cancer cell line A2780-CP70 as well as the non-resistant line A2780. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - April 17, 2020 Category: Chemistry Source Type: research

SNX-2112, an Hsp90 inhibitor, suppresses cervical cancer cells proliferation, migration, and invasion by inhibiting the Akt/mTOR signaling pathway
This study aimed at exploring the effects of SNX-2112 on the migration and invasion of cervical cancer cells and revealing the underlying molecular mechanisms. We found that SNX-2112 significantly decreased the viability, colony formation ability, and migration of HeLa and U14 cells. The invasiveness of HeLa cells and the proteins involved in metastasis were markedly reduced after SNX-2112 treatment. SNX-2112 inactivated the focal adhesion kinase (FAK) and inhibited the expression levels of matrix metallopeptidase (MMP)-9, MMP-2, SLUG, SNAIL, β-catenin, and Vimentin. Furthermore, SNX-2112 inhibited the protein kinase ...
Source: Medicinal Chemistry Research - April 17, 2020 Category: Chemistry Source Type: research

Synthesis and antiviral activity of some pyrrolonyl substituted heterocycles as additives to enhance inactivated Newcastle disease vaccine
AbstractThis research reported the design and synthesis of some influential new pyrrolone derivatives bearing a pyrazole scaffold with the evaluation of their antiviral activity against Newcastle disease virus (NDV) in specific pathogen free (SPF) chicken embryos and immune boosting properties of these substances in SPF chicks. The building block synthon was the pyrazolyl acid hydrazide, derived from 2(3H)-furanone, which was reacted with some carbonyl compounds, e.g., salicylaldehyde, furfural, 1,3-diphenylpyrazole-4-carbaldehyde, 2-chloroquinoline-3-carbaldehyde, chromone-3-carbaldehyde, and 3-acetylcoumarin. The results...
Source: Medicinal Chemistry Research - April 13, 2020 Category: Chemistry Source Type: research

Nrf2 activation through the inhibition of Keap1 –Nrf2 protein–protein interaction
AbstractActivation of the transcription factor Nrf2 via the Keap1 –Nrf2–ARE signaling system regulates the transcription and subsequent expression of cellular cytoprotective proteins and plays a crucial role in preventing pathological conditions exacerbated by the overproduction of oxidative stress. In addition to electrophilic modulators, direct noncovalent i nhibitors that interrupt the Keap1–Nrf2 protein–protein interaction (PPI) leading to Nrf2 activation have attracted a great deal of attention as potential preventive and therapeutic agents for oxidative stress-related diseases. Structural stud...
Source: Medicinal Chemistry Research - April 10, 2020 Category: Chemistry Source Type: research

Synthesis and cytotoxic evaluation of malachite green derived oleanolic and ursolic acid piperazineamides
AbstractThe coupling of acetylated piperazinylamide spacered triterpenoic oleanolic acid and ursolic acid withmeta orpara substituted carboxylated malachite green analogs gave conjugates10,11,15, and16 that were cytotoxic for several human tumor cell lines. Especially, an oleanolic acid-derived compound10 was cytotoxic for MCF-7 human breast carcinoma cells (EC50 = 0.7 μM). These derivatives represent first examples of triterpenoic acid derivatives holding a cationic scaffold derived from malachite green. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - April 9, 2020 Category: Chemistry Source Type: research

Design and synthesis of sulphonyl acetamide analogues of quinazoline as anticancer agents
AbstractA series of sulphonyl acetamide analogues were generated on the quinazoline ring through a multistep reaction starting from 2-mercapto-3H-quinazolin-4-one. The library of synthesised analogues was screened for in vitro cytotoxic activity against various human cancer cell lines such as HCT-1 and HT-15 (colon), MCF-7(Breast), PC-3 (Prostrate), SF268 (CNS) using MTT method. From the bioassay results, it was observed that even though most of the synthesised derivatives exhibited a good potency against various screened cancer cell lines, but compound10d, 10k, and10n were found to show very potent anticancer activity on ...
Source: Medicinal Chemistry Research - March 25, 2020 Category: Chemistry Source Type: research

Anticancer activity evaluation of indazolyl-substituted piperidin-4-yl-aminopyrimidines
AbstractBased on our previous work, a series of indazolyl-substituted piperidin-4-yl-aminopyrimidines, which were firstly used as anti-HIV agents, were evaluated for their anticancer potency in five cancer cell lines. Notably, they exhibited excellent activities with IC50 values ranging from 2.29 to 22.89  μM in H1975 cells, among which6c –e displayed lower cytotoxicity to normal lung cells than gefitinib. Furthermore, the typical compound6e, which was fourfold more potent than gefitinib in H1975 cell line, was tested for its ability to inhibit H1975 cell migration. The results revealed that6e showed superi...
Source: Medicinal Chemistry Research - March 20, 2020 Category: Chemistry Source Type: research

Phytochemicals and biological activities of species from the genus Maytenus
AbstractMaytenus is a genus in the plant family Celastraceae, the species of which are primarily distributed in China, Brazil, Uruguay, Paraguay, and northern Argentina. These plants have long been used as a resource for the development of medicines. The latest advances in the pharmacology and phytochemistry ofMaytenus are reviewed in this paper. Studies have discovered thatMaytenus spieces have efficacy in the treatment of various diseases. They are widely used as antitumor, anti-septicaemia, anti-inflammatory, analgesic, antibacterial, antioxidative, antiulcer, antipathogenic, anti-proliferative and salivation-inducing d...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

In vitro anticancer activity of pyrano[3, 2- c ]chromene derivatives with both cell cycle arrest and apoptosis induction
AbstractA series of 2-amino-4-aryl-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (4a–m) were synthesized via a one-pot three component condensation reaction between 4-hydroxy-2H-chromen-2-one, various aryl aldehydes and malononitrile in the presence of piperidine as a catalyst in ethanol under microwave irradiation conditions, with good to excellent yields. The structure elucidations of all the synthesized compounds were accomplished by spectral data, IR,1H NMR,13C NMR, MS, and elemental analyses. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer c...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Systematic understanding of the potential targets and pharmacological mechanisms of acteoside by network pharmacology approach
In this study, we aimed to predict the potential targets and pharmacological mechanisms of ACT via network pharmacology strategy and provide scientific evidence of drug discovery. The druglikeness of ACT was measured using the TCMSP database, and its potential targets were identified by both of ChemMapper and PharmMapper based on 3D-structure similarity. By mapping the potential targets obtained from ChemMapper and PharmMapper, the intersecting targets were screened as candidate targets. GO classification, pathway enrichment analysis, and drug –target–pathway networks were constructed to give a visual view. In ...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Pharmacophore modeling, atom-based 3D-QSAR and molecular docking studies on N -benzylpyrimidin-4-amine derivatives as VCP/p97 inhibitors
In this study, the atom-based three-dimensional quantitative structure –activity relationship (3D-QSAR) and docking models were developed using PHASE and GLIDE modules of Schrödinger software, respectively. The theoretical models were generated from 38N-benzylpyrimidin-4-amine inhibitors of p97. An AADRRR model consisting of two hydrogen bond acceptors (A), one hydrogen bond donor (D), and three aromatic rings (R) was obtained. Thirty eight derivatives were divided into a training set with 27 molecules to generate 3D-QSAR models and a test set with 11 molecules to validate 3D-QSAR model. A robust QSAR model with...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Repression of the transcriptional activity of ERR α with sequence-specific DNA-binding polyamides
In this study, we evaluated the potential for a pyrrole-imidazole polyamide to block ERR α binding to ERREs to inhibit gene expression. We demonstrated that the ERRE-targeted polyamide 1 blocked the binding of ERRα to the consensus ERRE and reduced the transcriptional activity of ERRα in cell culture. We further showed that inhibiting ERRα transcriptional activity with polyamide 1 l ed to reduced mitochondrial oxygen consumption, a primary biological effect regulated by ERRα. Finally, our data demonstrated that polyamide 1 is an inhibitor for cancer cell growth. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Synthesis and biological evaluation of fluorescent GAT-ligands based on asymmetric substituted BODIPY dyes
AbstractThe present study aimed at the development of fluorescent inhibitors addressing the GABA transporters mGAT1 –mGAT4 as potential tool compounds in fluorescence based biological assays. The design of these fluorescent GAT inhibitors followed the structural motifs common for many GAT1–GAT4 inhibitors publicly known except that the lipophilic domain present in this compounds was replaced by a BODIPY moiet y to serve as a fluorescent subunit. The fluorescent compounds obtained that way were tested for their inhibitory potencies and subtype selectivities at the four murine GABA transporter subtypes mGAT1&ndas...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Green synthesis, antitubercular evaluation, and molecular docking studies of ethyl 3,5-dicyano-6-oxo-2,4-diarylpiperidine-3-carboxylate derivatives
AbstractA simple and environment friendly one-pot synthesis of ethyl 3,5-dicyano-6-oxo-2,4-diarylpiperidine-3-carboxylate derivatives from aryl aldehydes, ethyl cyanoacetate, and ammonium acetate was developed in aqueous medium without using a catalyst. The significant features of this method are easy, inexpensive experimental procedures with short reaction time and high yield. The use of water as the solvent without catalyst makes the reaction meritorious and further fulfilled green chemistry protocols. The compounds were screened for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 25923) and ...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Anticonvulsant activity of new 3- and 4-benzoilpiridines oxime derivatives in comparison with valproic acid
AbstractThe aim of the research was to study the wide range of anticonvulsant effects of new 3- and 4-benzoylpyridines oxime derivatives in comparison with the reference drug valproic acid, it included assessment of motor and EEG convulsive state manifestations and epileptic status. To identify the most effective compound we studied the anticonvulsant effects in the models of generalized convulsions caused by maximal electroshock seizure test and subcutaneous administration of pentylenetetrazole. Later, the most active compound was studied in the models of chronic cobalt-induced epilepsy and epileptic status caused by neur...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Anticoagulant activity screening of an in-house database of natural compounds for discovering novel selective factor Xa inhibitors; a combined in silico and in vitro approach
AbstractTraditional edible natural products enclose a wealth of anticoagulants that can be prospected for new selective factor Xa inhibitors. Unlike multitargeted anticoagulants, selective factor Xa inhibitors effectively block coagulation cascade with a broader therapeutic window. In the present study, an in-house database comprises 3D structures of 1571 compounds from 26 natural products previously reported to enhance the bleeding tendency was compiled. Virtual screening (VS) of the constructed database to discover active FXa inhibitors was performed using sequential structure-based VS by Glide extra precision docking fo...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Targeted selective degradation of Bruton ’s tyrosine kinase by PROTACs
AbstractBruton ’s tyrosine kinase (BTK) is critical for B-cell receptor signaling and related to many types of human cancers. However, the drug resistance and off-target effect of present traditional BTK inhibitors occurred over time. As a new strategy for drug development, the proteolysis targeting chimera (PRO TAC) has been proved to target varieties of proteins. Here SPB5208 (4-(2-(2-(2-(2-(3-(4-amino-3-(4-phenoxy phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)ethoxy)ethoxy)ethoxy)ethoxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione) was synthesized as a new PROTAC degradation agent of BTK b y linking...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

A new pimarane-type diterpene obtained by biotransformation inhibits human HCT-116 colorectal carcinoma through inhibition of LTA 4 H activity
In this study, a new pimarane-type diterpene, namely, 8,15R-epoxy,16-hydroxy-pimaran-19-oic acid1 was obtained from the biotransformation of 8β-hydroxypimar-15-en-19-oic acid2 using a filamentous fungus,Cordyceps sinensis. Both compounds were in vitro tested for their cytotoxic effects against human colorectal carcinoma (HCT-116) cells. In addition, their selectivity was examined using the normal human fibroblast cells, HF-19 and TIG-1. The new metabolite1 exhibited potent cytotoxic activity against HCT-116 (IC50 7.53  μM) with no cytotoxicity against TIG-1 and HF-19. Thus, LTA4H inhibitory activity includin...
Source: Medicinal Chemistry Research - March 19, 2020 Category: Chemistry Source Type: research

Biologically active quinazoline-based hydroxamic acids
AbstractMolecular hybridization has become a new promising way to treat multifactorial diseases with a single compound that acts on multiple targets. The combination of several functional pharmacophore groups in one molecule can lead to a stronger therapeutic effect due to the ability to bind to several targets and possible synergistic interactions. The concept of multifunctional agents is being actively developed and has already produced some encouraging results. The quinazoline cycle and hydroxamic acids are unique pharmacophore groups that contribute to the structure of drug agents widely used in medical chemistry. The ...
Source: Medicinal Chemistry Research - March 18, 2020 Category: Chemistry Source Type: research

New phthalimide-benzamide-1,2,3-triazole hybrids; design, synthesis, α -glucosidase inhibition assay, and docking study
AbstractA new series of phthalimide-benzamide-1,2,3-triazole hybrids8a –k asα-glucosidase inhibitors was designed and synthesized. The biological evaluation of compounds8a –k against yeastα-glucosidase demonstrated that all they have excellent inhibitory activity in comparison with standard inhibitor acarbose. Among them, the most potent compound was compound8d with inhibitory activity 18.5-fold more than acarbose. Kinetic study revealed thatα-glucosidase inhibition of compound8d was the competitive type. Furthermore, docking study suggested that compound8d is more stable than acarbose in the ...
Source: Medicinal Chemistry Research - March 16, 2020 Category: Chemistry Source Type: research

Computational approach to the discovery of potential neprilysin inhibitors compounds for cardiovascular diseases treatment
AbstractNeprilysin (NEP, EC: 3.4.24.11) is an enzymatic membrane protein considered the prototype of the M13 zinc metallopeptidase family. Inhibitors of this enzyme constitute therapeutic targets for cardiovascular diseases. In spite of the existing alternatives for the treatment of these pathologies, the quality of life and the prognosis of the patients remain precarious, so the discovery of new drugs is required for this purpose. In this sense, in silico methods play a fundamental role, since they are an alternative to the traditional “trial and error” methods for obtaining new molecular entities. Taking into...
Source: Medicinal Chemistry Research - March 14, 2020 Category: Chemistry Source Type: research

Synthesis and biological effects of naphthalene-chalcone derivatives
AbstractIn this paper, 21 naphthalene-chalcone derivatives were synthesized and their biological effects were evaluated. The results showed that compounds2a –2u displayed clear antidepressant activity at 30  mg/kg in the forced swimming test. Compounds2h,2o,2t, and2u exhibited a good antidepressant effect in the forced swimming test and tail suspension test at 30  mg/kg. Compounds2h,2o,2t, and2u but had no effect on locomotor activity in the open-field test in mice. In addition, the most antidepressant activity of compound2o is likely mediated by increased serotonin and norepinephrine levels in central ...
Source: Medicinal Chemistry Research - March 13, 2020 Category: Chemistry Source Type: research

Selective cyclooxygenase-2 inhibitors: A review of recent chemical scaffolds with promising anti-inflammatory and COX-2 inhibitory activities
AbstractSelective cyclooxygenase-2 (COX-2) inhibitors have exhibited notable medicinal importance. In recent years, the discovery of new anti-inflammatory agents as selective COX-2 inhibitors has acquired more attention. This is due to the fact that currently available COX-2 inhibitors are linked with adverse effects. Various new organic scaffolds are being explored as new COX-2 inhibitors. In this review, we have mainly described different chemical scaffolds which have been investigated for COX-2 inhibition and anti-inflammatory activity. In the current review, literature from the last 10 years has been included. It will ...
Source: Medicinal Chemistry Research - March 9, 2020 Category: Chemistry Source Type: research