Ginkgolide B derivative synthesis and their effects on the viability of SKOV3 cells
AbstractThe natural product Ginkgolide B was used as a raw material and modified by esterification on C10-OH or C1-OH to obtain 11 derivatives (1–11), which were structurally characterized with nuclear magnetic resonance spectroscopy. An MTT assay-based in vitro tumor proliferation inhibitory activity test showed that compounds2,3,6,7,10, and11 exhibited strong inhibitory activity against the human ovarian cancer cells SKOV3, with IC50 values of 16.05  µmol/L, 15.65 µmol/L, 32.00 µmol/L, 63.30 µmol/L, 23.20 µmol/L, and 31.10 µmol/L, respect...
Source: Medicinal Chemistry Research - May 7, 2021 Category: Chemistry Source Type: research

Quinoxaline 1,4-di- N -oxides: a review of the importance of their structure in the development of drugs against infectious diseases and cancer
AbstractQuinoxaline 1,4-di-N-oxides (QdNO ’s) are potent drugs used since the middle of the last century as food additives to improve animal growth; however, their use as antibacterial agents led to an interest in investigating their mechanism of action, discovering that this heterocycle can cause DNA damage. Consequently, many molecules with different applications have been developed, with most of the research focused on studying their action as antibiotics, antifungals, antiparasitics, antituberculous, and anticancer agents. This review aims to present a condensate of the leading QdNO’s derivatives, as well a...
Source: Medicinal Chemistry Research - May 5, 2021 Category: Chemistry Source Type: research

Design, synthesis, and evaluation of potential carbamate prodrugs of 5 ′-methylthioadenosine (MTA)
Abstract5 ′-Methylthioadenosine (MTA) is a natural substrate of MTA phosphorylase (MTAP) and is converted to adenine via a salvage pathway for AMP production in normal healthy cells. The lack of MTAP expression in many solid tumors and hematologic malignancies compared to normal healthy cells has been explo red in a potential therapeutic strategy to selectively target tumor cells using antimetabolites such as 5-fluorouracil (5-FU) and 6-thioguanine (6-TG) while protecting normal healthy cells with MTA. Herein, a series of carbamate prodrugs, namely theN-(alkyloxy)carbonyl-MTA derivatives2a-f, was designed, synthesize...
Source: Medicinal Chemistry Research - April 29, 2021 Category: Chemistry Source Type: research

2-(3-Hydroxybenzyl)benzo[ d ]isothiazol-3(2 H )-one Mannich base derivatives as potential multifunctional anti-Alzheimer ’s agents
AbstractA series of 2-(3-hydroxybenzyl)benzo[d]isothiazol-3(2H)-one Mannich base derivatives were designed as potential multifunctional agents against Alzheimer ’s disease. The twelve derivatives were synthesized and evaluated with various biological activities. In vitro, biological assays showed that most of the target compounds are selective AChE inhibitors and good antioxidants. Among them, compounds 6d and 13d are representative agents exhibiting sign ificant selective AChE inhibition (IC50 = 1.09 µM and 2.01 µM, respectively), potent antioxidant activity, moderate inhibiti...
Source: Medicinal Chemistry Research - April 28, 2021 Category: Chemistry Source Type: research

Synthesis of arylfuran derivatives as potential antibacterial agents
AbstractBacterial infections represent a serious health care problem mainly due to the misuse and overuse of antibiotics, with consequent emergence of multidrug resistant bacterial strains. Then, because the urgent need to find novel and alternative antibacterial agents, the present work focuses on the synthesis of arylfuran derivatives with potential antimicrobial activity. Eighteen arylfuran derivatives were synthesized and evaluated for their antibacterial activity againstStaphylococcus aureus,Escherichia coli andPseudomonas aeruginosa. Among them, seven compounds containing an amino group in their structure showed acti...
Source: Medicinal Chemistry Research - April 27, 2021 Category: Chemistry Source Type: research

Design, synthesis, antibacterial evaluation and molecular docking studies of novel pyrazole/1,2,4-oxadiazole conjugate ester derivatives
AbstractThe development of new antimicrobial drugs is most needed due to rapid growth in global antimicrobial resistance. Thus, in this context, a series of novel pyrazole/1,2,4-oxadiazole conjugate ester derivatives (7a –j) was synthesized. All the derivatives were evaluated for their in vitro antibacterial activity against Gram-positive (Enterococcus, Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Salmonella, Klebsiella and Escherichia coli) bacteria and their minimum inhibitory concentration (MIC) was determined. Some of the derivatives have shown significant biological activity with a potency com...
Source: Medicinal Chemistry Research - April 27, 2021 Category: Chemistry Source Type: research

Callistemon genus- a review on phytochemistry and biological activities
AbstractCallistemon is an important genus in the family Myrtaceae which contains about 34 species. The members of this genus are known for their ornamental potentials, in addition to their outstanding value in conventional medicine in many parts of the world. Updated chemical analysis of theCallistemon genus has provided a variety of essential phytocompounds belonging to different chemical classes including terpenes, phenolic derivatives, flavonoids, anthocyanins, neolignans, phloroglucinol derivatives and other miscellaneous compounds. Hence, this dissertation reflects a systematic evaluation of theCallistemon genus phyto...
Source: Medicinal Chemistry Research - April 27, 2021 Category: Chemistry Source Type: research

Recent advances in chemical reactivity and biological activities of eugenol derivatives
AbstractEugenol (4-allyl-2-methoxyphenol) is a volatile phenolic bioactive compound derived from a natural resource. This compound has been identified in several aromatic plants, among whichSyzygium aromaticum (L.) Merr. and L.M. Perry contains between 45 and 90% of eugenol in its essential oil compared to other natural sources. Eugenol has been studied over the years and has shown to display a wide range of biological activities as antifungal, antimicrobial, anti-inflammatory, antioxidant, analgesic, anticancer, and antiparasitic. It has been extensively used in cosmetics, in food processing industry, and also as a starti...
Source: Medicinal Chemistry Research - April 27, 2021 Category: Chemistry Source Type: research

Syntheses and anticancer activities of novel glucosylated ( −)-epigallocatechin-3-gallate derivatives linked via triazole rings
AbstractNovel glucosylated (-)-epigallocatechin-3-gallate derivatives10–13 having the EGCG analogs conjugated to thed-glucosyl azide were synthesized by carrying out the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and were evaluated for their cytotoxicities against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) using MTT assays. Compounds10 and11 showed the highest levels of cytotoxicity against the HL-60 cells with IC50 values of 4.57 and 3.78  μM, respectively, and showed moderate selectivity toward cancer cell lines. Compound11 was also shown to indu...
Source: Medicinal Chemistry Research - April 26, 2021 Category: Chemistry Source Type: research

A comparative study of the recent most potent small-molecule PD-L1 inhibitors: what can we learn?
AbstractImmune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have become a “game-changer” in the cancer treatment. However, none of the small molecular inhibitors has been approved yet. To explore the advantages and disadvantages of various scaffolds, different biological evaluations were performed on the three selected small inhibitors, namely Incyte-001, Incyte-011, and BMS-1001. In the HTRF assay, BMS-1001 showed the best binding activity for PD-L1 (IC50 = 0.9 nM) while Incyte-011 (IC50 = 5.293 nM) was twice more potent than the Incyte-001 (IC50 =&thi...
Source: Medicinal Chemistry Research - April 13, 2021 Category: Chemistry Source Type: research

Synthesis, molecular docking, and biological evaluation of nitroimidazole derivatives as potent urease inhibitors
The objective of this study was to design new nitroimidazole-based derivatives as strong urease inhibitors for the treatment ofH. pylori infections. New series of nitroimidazole derivatives,4a –k, were synthesized by using TBTU as the catalyst and assayed as Jack bean urease inhibitors. The facile synthetic approach was employed for the preparation of targeted molecular designs in good to excellent yields, ranged from 65 to 92%. Accordingly, all the synthesized compounds,4a –k (IC50 = 1.43–7.72 μM), were more potent than the standard urease inhibitors, thiourea, and hydroxyurea. Am...
Source: Medicinal Chemistry Research - April 12, 2021 Category: Chemistry Source Type: research

Diversifying the xanthine scaffold for potential phosphodiesterase 9A inhibitors: synthesis and validation
This study divulged the reactivity pattern of three –NH groups at N1, N3 and N7 position of xanthine in the order of N7 >  N3 >  N1, which helped in carrying out regio-selective N-alkylation reaction at different –NH sites of xanthine. Selective protection and selective deprotection at N3 and/or N7 sites of xanthine were the key strategies for developing two synthesis schemes. Eight newly synthesized compoundsC1-8 were evaluated for their biological activity against Phosphodiesterase 9A. All the compounds were found to be promising inhibitors. To gain further insight for mode o...
Source: Medicinal Chemistry Research - April 10, 2021 Category: Chemistry Source Type: research

Dual monoamine oxidase B and acetylcholine esterase inhibitors for treating movement and cognition deficits in a C. elegans model of Parkinson ’s disease
AbstractParkinson ’s disease (PD) is an age-associated neurodegenerative movement disorder that leads to loss of dopaminergic neurons and motor deficits. Approaches to neuroprotection and symptom management in PD include use of monoamine oxidase B (MAO-B) inhibitors. Many patients with PD also exhibit memory loss i n the later stages of disease progression, which is treated with acetylcholine esterase (AChE) inhibitors. We sought to identify a dual-mechanism compound that would inhibit both MAO-B and AChE enzymes. Our screen identified a promising compound (7) with balanced MAO-B (IC50 of 16.83  µM) and ...
Source: Medicinal Chemistry Research - April 9, 2021 Category: Chemistry Source Type: research

Sulfamate-tethered aza -Wacker approach towards analogs of Bactobolin A
AbstractHere, we describe an approach towards analogs of the potent antibiotic Bactobolin A. Sulfamate-tetheredaza-Wacker cyclization reactions furnish key synthons, which we envision can be elaborated into analogs of Bactobolin A. Docking studies show that the C4 epimer of Bactobolin A and the C4/C6 diastereomer interact with different residues of the 23S rRNA (bacterial ribosome 50S subunit) than the natural product, suggesting that these molecules could be valuable tool compounds for fundamental studies of the bacterial translational machinery. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - April 6, 2021 Category: Chemistry Source Type: research

Natural products and their derivatives as anti- flavivirus drug candidates
AbstractFlavivirus is a genus that comprises more than 70 viruses with common characteristics and causes many of the most prevalent infections in the world. These viruses affect more people than any other genus. However, compared to other viral diseases, priorities are low in the context of public health perhaps due to their prevalence in developing countries. A safe and efficacious vaccine would be the ideal way to prevent diseases caused byFlavivirus spp., however, the treatment of most of these infections is still nonspecific and symptomatic. Natural products and their derivatives are emerging as candidates in the treat...
Source: Medicinal Chemistry Research - April 3, 2021 Category: Chemistry Source Type: research

New synthetic 1 H -1,2,3-triazole derivatives of 3- O -acetyl- β-boswellic acid and 3- O -acetyl-11-keto-β-boswellic acid from Boswellia sacra inhibit carbonic anhydrase II in vitro
AbstractBoswellic acids are genus specific toBoswellia; they are the principal biologically active compounds holding exceptionally potent anti-inflammatory activity. A series of new 1H-1,2,3-triazole tethered of 3-O-acetyl- β-boswellic acid (ABA,1) and 3-O-acetyl-11-keto- β-boswellic acid (AKBA,2) derivatives (10a-d and11a-d) were synthesized and their carbonic anhydrase II (CA II) inhibitory activity was evaluated in vitro. The structures of all compounds were confirmed by1H-,13C-NMR, and HR-MS spectral data (10b, 10c and11b, 11c). The series displayed a moderate to significant inhibition against CA II with IC50...
Source: Medicinal Chemistry Research - March 31, 2021 Category: Chemistry Source Type: research

Synthesis, docking, and biological evaluation of thiazolidinone derivatives against hepatitis C virus genotype 4a
AbstractHepatitis C virus (HCV) genotype 4a (GT4a) is prevalent in Egypt. It did not gain the necessary scientific focus despite its high resistance. Since the crystal structure NS5B (RNA-dependent RNA polymerase) of HCV GT4a has not been resolved until now, homology modeling was conducted to build and validate the 3D model of the enzyme. Ligand binding sites including the allosteric thumb II pocket were detected and used in lead optimization. Sixty new 4-thiazolidinone derivatives have been virtually designed and docked into thumb II site of HCV NS5B GT4a using rigid docking approach. Eighteen compounds (7a –r) that...
Source: Medicinal Chemistry Research - March 26, 2021 Category: Chemistry Source Type: research

Synthesis and antitumor activity of novel pyridoxine-based structural analogs of saccharumoside-B
AbstractA series of 11 new pyridoxine-based structural analogs of saccharumoside-B were obtained using original synthetic approach. Antitumor activity of these compounds against nine human tumor cell lines (MCF-7, MDA-MB-231, A-498, SNB-19, M-14, NCI-H322M, HCT-115, HCT-116, and PC-3) was studied, and cytotoxic activity to three normal (HEK-293, Chang Liver, and MSC) cell lines was evaluated. Among the synthesized compounds,12d, 12e,13b, 13d,13e, and14 exhibited the highest antitumor activity, comparable to that of camptothecin and doxorubicin, but with significantly increased selectivity toward tumor cells. (Source: Medic...
Source: Medicinal Chemistry Research - March 25, 2021 Category: Chemistry Source Type: research

Design and synthesis of new 1,4,5-trisubstituted triazole-bearing benzenesulphonamide moiety as selective COX-2 inhibitors
AbstractA new series of 1,4,5-trisubstituted triazole-bearing benzenesulphonamide moiety, COX-2 pharmacophore, was designed and synthesized. The synthetic pathway for preparation of the new 1,2,3-triazole derivatives started with the preparation of the two key intermediates: 4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)benzenesulfonamide3 and 4-(4-(hydrazinecarbonyl)-5-methyl-1H-1,2,3-triazol-1-yl)benzenesulfonamide13 that were then used to synthesize the new triheterocycles. All the synthesized compounds were virtually screened for their binding interactions with both COX isozymes. Compounds showing similar conformation to ...
Source: Medicinal Chemistry Research - March 23, 2021 Category: Chemistry Source Type: research

Selectivity and potency of natural product PIM kinase inhibitors identified by in silico docking
AbstractPIM3 (Proviral Integration site for Maloney murine leukemia virus kinase 3) is a proto-oncogene with serine/threonine kinase activity that prevents apoptosis, promotes cell survival, and stimulates protein translation. In addition, PIM3 functions in inflammation and immunity pathways. PIM3 inhibitors are being developed to treat cancer and inflammation-related disorders. Here we screen a 98,000 compound virtual library of natural products to identify those that are predicted to fit in the ATP site of PIM3. Since the structure of PIM3 has not been determined experimentally, we performed molecular structure predictio...
Source: Medicinal Chemistry Research - March 17, 2021 Category: Chemistry Source Type: research

Loading harmine on nanographene changes the inhibitory effects of free harmine against MCF-7 and fibroblast cells
In this study, harmine was loaded on FA-NGO (FA-NGO/harmine) viaπ–π stacking and hydrophobic interactions and the cytotoxicity against MCF-7, as FR positive cancerous cell, and fibroblast cells, as normal FR negative cell, were investigated. The in vitro studies illustrated that FA-NGO/harmine have remarkably higher cytotoxicity against MCF-7 cells, about 60% cell loss, in comparison with free harmine with 40% cell loss (in the concentration of 40  μg mL−1). However, the released amount of harmine into normal fibroblast cells was considerably low, only 28% cell loss in dose of 40  ...
Source: Medicinal Chemistry Research - March 16, 2021 Category: Chemistry Source Type: research

Design, synthesis, and biological evaluation of pyrimidine analogs as SecA inhibitors
AbstractSecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. We have previously reported pyrimidine analogs as SecA inhibitors. Herein, we report an extension of the earlier work in the synthesis and evaluation of a series of 15 5-cyanothiouracil derivatives as SecA inhibitors. All the compounds have been evaluated for their inhibition of SecA ATPase (EcSecAN68) and for their antimicrobial activity againstEscherichia coli NR698 (a leaky mutant) andBacillus anthracis Sterne. Twelve compounds showed IC50 of less than 6.3  μM...
Source: Medicinal Chemistry Research - March 12, 2021 Category: Chemistry Source Type: research

Phenylpropanoids from Liparis nervosa and their in vitro antioxidant and α-glucosidase inhibitory activities
In conclusion, the present study suggests that phenylpropanoids may be the additional representative type of active constituents inL. nervosa, which provides a new line of evidence to understand this medicinal plant. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - March 10, 2021 Category: Chemistry Source Type: research

n -Propyl 6-amino-2,6-dideoxy-2,2-difluoro- β- d -glucopyranoside is a good inhibitor for the β-galactosidase from E. coli
AbstractA convenient route has been developed for the synthesis of novel 6-amino-2,2-(or 3,3-difluoro)-2-(or 3),6-dideoxy-hexopyranoses. Biological screening showed these compounds as good inhibitors for several glycosidases. Especiallyn-propyl 6-amino-2,6-dideoxy-2,2-difluoro- β-d-glucopyranoside (8) was an excellent competitive inhibitor for the β-galactosidase fromE. coli holding aKi of 0.50  μM. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - March 5, 2021 Category: Chemistry Source Type: research

Synthesis, characterization, crystal structures, and anticancer activity of some new 2,3-dihydro-1,5-benzoxazepines
AbstractVarious benzoxazepine derivatives have been synthesized and characterized using IR, NMR, GC –MS, and microanalysis. The single-crystal X-ray structures of 2,2-dimethyl-4-[(E)-2-(4-methylphenyl)ethenyl]-2,3-dihydro-1,5-benzoxazepine (RS01),4-[(E)-2-(2-chlorophenyl)ethenyl] -2,2-dimethyl-2,3-dihydro-1,5-benzoxazepine (RS05),2,2,4-trimethyl-2,3-dihydrobenzothiazepine (RS11), and2,2,4-trimethyl-2,3-dihydrobenzoxazepine (RS12) have been discussed. The compounds have been evaluated for their anticancer properties in breast cancer cells.4-[(E)-2-(2-Chlorophenyl)ethenyl]-2,2-dimethyl-2,3-dihydro-1,5-benzoxazepine (RS...
Source: Medicinal Chemistry Research - February 11, 2021 Category: Chemistry Source Type: research

Structural modeling and analysis of the SARS-CoV-2 cell entry inhibitor camostat bound to the trypsin-like protease TMPRSS2
AbstractThe type II transmembrane serine protease TMPRSS2 facilitates the entry of coronaviruses, such as SARS-CoV-2, into host cells by cleaving the S1/S2 interface of the viral spike protein. Based on structural data derived from X-ray crystallographic data of related trypsin-like proteases, a homology model of TMPRSS2 is described and validated using the broad spectrum COVID-19 drug candidate camostat as a probe. Both active site recognition and catalytic function are examined using quantum mechanics/molecular mechanics molecular dynamic (QM/MM MD) simulations of camostat and its active metabolite, 4-(4-guanidinobenzoyl...
Source: Medicinal Chemistry Research - February 5, 2021 Category: Chemistry Source Type: research

Evaluation of 3-carbamoylpropanoic acid analogs as inhibitors of human hypoxia-inducible factor (HIF) prolyl hydroxylase domain enzymes
We describe the synthesis of 3-carbamoylpropanoic acid derivatives and their evaluation as human PHD-2 inhibitors. MS assays indicated that derivatives with a 3-carbamoylpropanoic acids-containing benzoxazole moiety are inhibitors of PHD-2 with IC50 values of 2.24  μM and 1.32 μM, respectively. However, neither the acids nor their respective ethyl esters were observed to upregulate HIF-1α levels in cells. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - February 3, 2021 Category: Chemistry Source Type: research

Synthesis and biological evaluation of pyrrolidine-functionalized nucleoside analogs
AbstractInhibition of viral reverse transcriptases and mammalian DNA polymerases by unnatural nucleoside analogs is a proven approach in antiviral and anticancer therapy, respectively. The majority of current nucleoside drugs retain the canonical nucleobase structure, which is fused to an unnatural sugar. In the present work, a series of novel pyrrolidine-functionalized purine and pyrimidine nucleosides was prepared via PyBOP-catalyzed SNAr addition-elimination reactions of commercial halogenated precursors and tested for their antiviral and anticancer activity. The newly synthesized nucleoside analogs showed limited biolo...
Source: Medicinal Chemistry Research - February 3, 2021 Category: Chemistry Source Type: research

Phthalamide derivatives as ACE/AChE/BuChE inhibitors against cardiac hypertrophy: an in silico, in vitro, and in vivo modeling approach
This study aimed to synthesize three phthalamide derivatives (M-01, M-02, and M-03) and evaluate them as three-target (ACE/AChE/BuChE) inhibitors with the possible dual effect of reducing hypertension and r everting cardiac hypertrophy. After in silico and in vitro experiments, one compound was tested in vivo on rats. All three phthalamides were synthesized in good yields, showing good competitive inhibition of the three-target enzymes in silico and in vitro. M-01 (10 mg/kg) significantly reversed ca rdiomyocite hypertrophy (by 87.3%;p 
Source: Medicinal Chemistry Research - February 3, 2021 Category: Chemistry Source Type: research

Isonicotinoyl hydrazones of pyridoxine derivatives: synthesis and antimycobacterial activity
AbstractA series of novel isonicotinoyl hydrazones based on pyridoxine (vitamin B6) were synthesized. The synthesized compounds were evaluated for their antimycobacterial activity onM. tuberculosis H37Rv strain. The most potent compound13 showed good activity on H37Rv strain and on clinical isolates ofM. tuberculosis with multidrug-resistant tuberculosis (TB) profile included first- and second-line drugs. Cytotoxicity studies of compound13 on human embryonic kidney cells, human liver, human mesenchymal stem cells, and human embryonic lung cells in vitro demonstrated it is 2 –3 times less toxicity then isoniazid and 1...
Source: Medicinal Chemistry Research - February 1, 2021 Category: Chemistry Source Type: research

Repositioning of Isatin hybrids as novel anti-tubercular agents overcoming pre-existing antibiotics resistance
AbstractThe widespread deaths of tuberculosis from many decades demands an urgent need for the development of novel anti-tubercular scaffolds that are more potent and highly selective with lower cytotoxicity. Isatin hybrids are endowed with an extensive range of biological activities. Hybridization of isatin with various heterocyclic moieties such as benzofuran, coumarin, tetrahydropyrimidine, quinoline, and well-known drugs like Moxifloxacin, Ciprofloxacin, and so on may provide promising anti-tubercular candidates. This review focuses on the recent developments of isatin-based hybrids possessing potential anti-tubercular...
Source: Medicinal Chemistry Research - January 30, 2021 Category: Chemistry Source Type: research

In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine
AbstractAzulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such asMatricaria chamomilla,Artemisia absinthium,Achillea millefolium, andLactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflamma...
Source: Medicinal Chemistry Research - January 30, 2021 Category: Chemistry Source Type: research

Adenosine receptors as promising targets for the management of ocular diseases
AbstractThe ocular drug discovery arena has undergone a significant improvement in the last few years culminating in the FDA approvals of 8 new drugs. However, despite a large number of drugs, generics, and combination products available, it remains an urgent need to find breakthrough strategies and therapies for tackling ocular diseases. Targeting the adenosinergic system may represent an innovative strategy for discovering new ocular therapeutics. This review focused on the recent advance in the field and described the numerous nucleoside and non-nucleoside modulators of the four adenosine receptors (ARs) used as potenti...
Source: Medicinal Chemistry Research - January 25, 2021 Category: Chemistry Source Type: research

Pentacyclic triterpene acid conjugated with mitochondria-targeting cation F16: Synthesis and evaluation of cytotoxic activities
AbstractThe first representatives of F16-conjugated pentacyclic triterpenoids, betulin and betulinic, ursolic, oleanolic, and glycyrrhetic acid derivatives, were synthesized. The triterpene core was linked, at the С-3, С-28, or С-30 position, to one or two mitochondria-targeting delocalized lipophilic cationsF16 via butane or triethylene glycol spacer. The human cancer cell lines U937 (leukemic monocyte lymphoma), K562 (chronic myeloid leukemia), and Jurkat (T-lymphoblastic leukemia), and a human nonmalignant fibroblast cell line were used to evaluate the cytotoxic activities of the products. Most of the obtained conjug...
Source: Medicinal Chemistry Research - January 25, 2021 Category: Chemistry Source Type: research

In honor of Professor Robert Vince on the occasion of his 80th birthday
(Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - January 23, 2021 Category: Chemistry Source Type: research

Synthesis and in vitro evaluation of triphenylphosphonium derivatives of acetylsalicylic and salicylic acids: structure-dependent interactions with cancer cells, bacteria, and mitochondria
In this study, effective synthesis of SA and acetylsalicylic acid (ASA) derivatives with a carrier triphenylphoshonium (TPP) group was proposed. A series of SA and ASA conjugates linked with the TPP group via alkyl chain linker (C3-C10) was synthesized. The conjugates showed enhanced TPP-mediated cytotoxicity towards MCF-7, Caco-2, PC-3 cells in proportion to the linker length.7e, 8e (C9), and7f (C10) were the most active against the cancer cells with IC50 = 0.6–1.9 µM while were less toxic for HSF. Similarly, antibacterial (bactericidal) activity of the compounds againstS. aureus increased...
Source: Medicinal Chemistry Research - January 21, 2021 Category: Chemistry Source Type: research

Tuberculosis: current scenario, drug targets, and future prospects
AbstractGlobally recognized genetic modification with time has supported the emergence of versatile and novel featured organisms in nature, some of which can be analogized with Pandora ’s box elements; likeMycobacterium sp. which has revived itself again after again in a repetitive order over decades and, gradually, contriving a red alert on the world health graph. It needs to be rectified with the motivation of new drug approval considering the pipe line moieties or, apt a choice from the existing drug genera. Although, with genetic modification and advancementMycobacterium tuberculosis has ruined the first-line the...
Source: Medicinal Chemistry Research - January 20, 2021 Category: Chemistry Source Type: research

Divalent tranylcypromine derivative as lysine-specific demethylase 1 inhibitor
AbstractTranylcypromine (TCP) is a useful pharmacophore for lysine-specific demethylase 1 (LSD1) inhibitors. Based on the mode of action (MOA) of TCP and structure of LSD1, divalent TCP derivatives with aliphatic and benzylic linkers were designed, synthesized, and evaluated for their LSD1 inhibitory activity, MV4-11 antiproliferative activity, and CD86 mRNA expression enhancement. All ten new compounds showed improved activity against LSD1 than TCP and GSK2879552. Several compounds with rigid aliphatic linkers demonstrated nanomolar enzymatic and cellular activities, as well as good MAO-A/B selectivity. Further supported ...
Source: Medicinal Chemistry Research - January 20, 2021 Category: Chemistry Source Type: research

γ- and δ-lactones as fumarate esters analogues and their neuroprotective effects
AbstractThe γ-butyrolactone and δ-valerolactone structural units are present in different natural products with significant pharmacological properties. Fumaric acid ester-based drugs are used for the treatment of psoriasis and, more recently, multiple sclerosis. We synthesized different γ-butyrolactone and δ -valerolactone derivatives where the fumarate moiety is forced into a lactone ring in search of strategies to maintain the anti-inflammatory activity of fumaric acid esters limiting the side effects and enhancing the bioavailability. The structures of all synthesized compounds obtained were iden...
Source: Medicinal Chemistry Research - January 16, 2021 Category: Chemistry Source Type: research

Novel 1-methoxyindole- and 2-alkoxyindole-based chalcones: design, synthesis, characterization, antiproliferative activity and DNA, BSA binding interactions
AbstractIndole-based chalcones have been identified as interesting compounds with anticancer properties. In the present study, we report the synthesis and evaluation of new 1-methoxyindole and 2-alkoxyindole chalcone hybrids as antiproliferative agents active against colorectal carcinoma cell line. Among the 19 investigated molecules, four inhibit the proliferation of colorectal cancer cells HCT-116 with IC50 values
Source: Medicinal Chemistry Research - January 16, 2021 Category: Chemistry Source Type: research

Anti-inflammatory scalarane-type sesterterpenes, erectascalaranes A –B, from the marine sponge Hyrtios erectus attenuate pro-inflammatory cyclooxygenase-2 and 5-lipoxygenase
AbstractChemical investigation of demospongeHyrtios erectus (family Thorectidae) resulted in the identification of two scalarane-type sesterterpenes, erectascalaranes A –B, which were characterized as 3-((but-35-enyloxy)methyl)-icosahydro-11-hydroxy-4,4,8,10,13-pentamethyl-20-oxochryseno[2,1-c]furan-12-yl acetate (erectascalarane A) and 3-((but-35-enyloxy)methyl)-hexadecahydro-11-hydroxy-4,4,8,10,13-pentamethylchryseno[2,1-c]furan-20(5bH)-one (erectascalarane B) using detailed spectroscopic experiments. Erectascalarane A exhibited significantly greater attenuation property against pro-inflammatory cyclooxygenase-2 (I...
Source: Medicinal Chemistry Research - January 15, 2021 Category: Chemistry Source Type: research

Sulfur-containing therapeutics in the treatment of Alzheimer ’s disease
This article provides a comprehensive review of organosulfur-based AD therapeutic agents and provides insights into their future development. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - January 15, 2021 Category: Chemistry Source Type: research

Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery
AbstractCurrently, the development of anticancer drug resistance is significantly restricted the clinical efficacy of the most commonly prescribed anticancer drug. Malignant disease is widely prevalent and considered to be the major challenges of this century, which concerns the medical community all over the world. Consequently, investigating small molecule antitumor agents, which could decrease drug resistance and reduce unpleasant side effect is more desirable. 2-aminothiazole scaffold has emerged as a promising scaffold in medicinal chemistry and drug discovery research. This nucleus is a fundamental part of some clini...
Source: Medicinal Chemistry Research - January 15, 2021 Category: Chemistry Source Type: research

Benzopyrylium salts as new anticancer, antibacterial, and antioxidant agents
AbstractBenzopyrylium salts are an unexplored class of compounds and as a first, this study reports them as potential therapeutic agents. In this effort we pursue the synthesis and in vitro anticancer, antibacterial and antioxidant properties of some novel benzopyrylium salts. The benzopyrylium salts were synthesized and further characterized via UV-vis, IR,1H-NMR,13C-NMR and mass spectrometry. The benzopyrylium salts were tested in vitro for anticancer activity across NCI 60 cell line panel.PS-CP-4MO showed the best activity against the MDA-MB-435 cell line of melanoma cancer in terms of the least GI50 (1.78  &micr...
Source: Medicinal Chemistry Research - January 13, 2021 Category: Chemistry Source Type: research

8-cyanobenzothiazinone analogs with potent antitubercular activity
Abstract8-Nitrobenzothiazinones (BTZs) exemplified by macozinone are a new class of antitubercular agents with exceptionally potent activity. The aryl nitro group has been considered indispensable for activity since this is bioactivated within mycobacteria by the flavoenzyme DprE1 to a reactive nitroso metabolite that covalently labels Cys387. However, the aryl nitro group is a potential liability with regards to safety, stability, and resistance. In this paper, we introduced a nitrile as a bioisosteric replacement of the nitro group, which we hypothesize can maintain a similar covalent mechanism of inhibition, but mitigat...
Source: Medicinal Chemistry Research - January 13, 2021 Category: Chemistry Source Type: research

Design and synthesis of newer N-benzimidazol-2yl benzamide analogues as allosteric activators of human glucokinase
AbstractAllosteric activators of human glucokinase (GK) had revealed significant hypoglycemic effects for therapy of type-2 diabetes (T2D) in animal as well as human models. Some newer N-benzimidazol-2yl substituted benzamide analogues were prepared and assessed for activation of GK accompanied by molecular docking investigations for predicting the bonding interactions of these derivatives with the residues in allosteric site of GK protein. Amongst the derivatives synthesized, compounds2 and7 strongly increased catalytic action of GK (GK activation fold>2.0 in comparison to control) in vitro. The results of in-vitro tes...
Source: Medicinal Chemistry Research - January 13, 2021 Category: Chemistry Source Type: research

N -(2,3,4,6-tetra- O -acetyl- β- d -glucopyranosyl)thiosemicarbazones of 6-alkoxy-2-oxo-2 H -chromene-4-carbaldehydes: synthesis, evaluation of their antibacterial, anti-MRSA, antifungal activity, and docking study
AbstractReaction of 6-alkoxy-2-oxo-2H-chromen-4-carbaldehydes withN-(2,3,4,6-tetra-O-acetyl- β-d-glucopyranosyl)thiosemicarbazide yielded corresponding thiosemicarbazones having 2H-chromen-2-one ring. In vitro evaluations showed that these 2H-chromen-2-one compounds exhibited remarkable antibacterial and antifungal activities against some typical bacteria and fungi. Representative compounds with MIC values of 0.78  − 1.56 μg/mL were6c,6g (againstS. aureus),6a,6f (againstS. epidermidis) (Gram-positive bacterial strains),6e,6g (againstE. coli),6b,6e (againstK. pneumoniae), and6d–f (ag...
Source: Medicinal Chemistry Research - January 13, 2021 Category: Chemistry Source Type: research

Structural insights of sulfonamide-based NLRP3 inflammasome inhibitors: design, synthesis, and biological characterization
AbstractNLRP3 inflammasome has recently attracted much attention as a potentially druggable target to develop potential therapeutics for inflammatory and neurodegenerative disorders. In our continuing studies, structure –activity relationship studies were conducted based on a newly identified NLRP3 inhibitor,YQ-II-128, from our laboratory to understand the structural features and improve aqueous solubility. The results revealed that steric interactions at the propoxyl and amide domain ofYQ-II-128 are important for the observed inhibitory potency on the NLRP3 inflammasome. The results also identified the amide domain ...
Source: Medicinal Chemistry Research - January 13, 2021 Category: Chemistry Source Type: research

DDR1 and DDR2: a review on signaling pathway and small molecule inhibitors as an anticancer agent
AbstractCancer is the 2nd most fatal disease around the globe. Various receptors have been showed to be overexpressed and/or mutated in numerous cancers. Discoidin domain receptors 1 (DDR1) and 2 (DDR2) are one of the novel receptor tyrosine kinases (RTKs), which have been proved to regulate various cellular signaling pathways, cell proliferation, adhesion, migration, matrix remodeling, and dysregulation of these receptors may lead to metastatic cancer progressions. These receptors belong to unique category of RTKs, which require collagen binding for its activation. Yet the mechanism of this extracellular collagen binding ...
Source: Medicinal Chemistry Research - January 12, 2021 Category: Chemistry Source Type: research

Synthesis and evaluation of benzenesulfonic acid derivatives as human neutrophil elastase (hNE) inhibitors
AbstractHerein we report our investigation concerning the development of Human neutrophil elastase (hNE) inhibitors for the treatment of Acute Respiratory Distress Syndrome (ARDS). Various benzenesulfonic acid derived compounds were synthesized and evaluated as competitive inhibitors of hNE. Biological screening revealed that compound4f shows moderate inhibitory activity (IC50 = 35.2 μM) against hNE. Compound4f was also superimposed onto the active center of hNE to understand the binding mode. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - January 12, 2021 Category: Chemistry Source Type: research