Mini Reviews in Medicinal Chemistry - Volume 19, Issue 5, 2019

Detailed critical analysis of publications devoted to QSPR of aqueous solubility is presented in the review with discussion of four types of aqueous solubility (three different thermodynamic solubilities with unknown solute structure, intrinsic solubility, solubility in physiological media at pH=7.4 and kinetic solubility), variety of molecular descriptors (from topological to quantum chemical), traditional statistical and machine learning methods as well as original QSPR models.

Microorganisms are able to produce hundreds of unique chemical structures that can be effectively used by the human beings on their own benefit using the products in the chemical industry. Bacteria belonging to Bacillus genera are very good chemical factories capable to synthesize different compounds with a wide variety of activities. In this review, we try to review the compounds with their respective biological activities produced by different species of Bacillus.

The incidence of diabetes mellitus (DM) is on the rise, worldwide. One of the main complications in DM is delayed wound healing and it often requires amputation. Various drugs were used to treat DM but they presented with adverse effects. Often, patients failed to comply with such treatment. This opened the door for complementary and alternative medicine. In the present review, we explored the molecular concept of wound healing occurring in different stages with special emphasis to DM. We also highlighted the potential herbal products such as NF3 (Chinese 2-Herb Formula), Zicao, Jing Wan Hong ointment, Aleo vera, mixture of Adiantum capillus-veneris, Commiphora molmol, Aloe vera, and henna, Phenol-rich compound sweet gel, Jinchuang ointment, San-huang-sheng-fu (S) oil, Yi Bu A Jie extract, Astragali Radix (AR) and Rehmanniae Radix (RR), Yiqi Huayu, Tangzu yuyang ointment, Shengji Huayu recipe, Angelica sinensis, Lithospermun erythrorhison, Hippophae rhamnoides L., Curcuma longa and Momordica charantia that could be used effectively to treat DM wounds. Future clinical trials are needed for designing potential drugs which may be effective in treating DM wounds.

Background: New aryl substituted cyclohepta[b]pyridine and cyclohepta[d]pyrimidine derivatives were synthesized. The sugar hydrazones of the synthesized pyridine and pyrimidine compounds were also prepared. Method: In addition, the 1,3,4-oxadiazolyl acyclic C-nucleoside analogs of the pyridine system were prepared. The hemolytic, prebiotic, anticancer and antimicrobial activities of some of the synthesized compounds were also studied. Compounds 10 and 12 showed high activity against MCF-7, HEPG-2 and HCT-116 cell lines with IC50 at range 3.56-8.55 μg/mL. In addition, the synthesized condensed thiopyrimidine derivative 10 exhibited more potent bactericidal activity while compound 7 demonstrated potent antifungal activity against Aspergillus niger. Furthermore, the synthetic compounds of the pyrimidine base promoted the growth of lactic acid bacteria. Results: The predicted binding patterns of three of the prepared derivatives as possible antagonists against ERα were investigated which showed good binding patterns.

Introduction: The signalling function of 2-arachidonoylglycerol (2-AG) in endocannabinoid system is delineated by Monoacylglycerol lipase (MAGL). MAGL readdresses the lipid stores in the direction of pro-tumorigenic signalling lipids in cancer cells. Selective as well as potent MAGL inhibitors are limited in number hence their continuous development may lead to a breakthrough invention in the field of MAGL inhibitors. In succession of the above, we have synthesised 2-amino-4- methylthiazole-5-carboxylate derivatives and characterised them by collective use of IR, 1H-NMR, 13C-NMR, Mass spectral data and elemental analysis. Methodology: Thirteen compounds (3c-g, 4c, 4e, 4f and 6b-f) inhibited MAGL with IC50 value 0.037- 9.60 μM. Two compounds (3g and 4c) were found to be most potent with IC50 values 0.037 and 0.063μM, respectively. Thirty synthesised compounds were sent to NCI for anticancer screening, out of which nine compounds were selected for one dose anticancer assay. Compounds 3g (NSC:788170) and 4c (NSC:788176)were found to be the most potent during one dose anticancer screening and fulfilled the specified threshold for growth inhibition criteria of NCI and were further selected for full panel five dose assay at 10-fold dilutions of five different concentrations. Conclusion: Compound 3g displayed GI50 value 0.865 μM against EKVX (Non-Small Cell Lung Cancer cell line), and 1.20 μM against MDA-MB-468 (Breast Cancer cell Line), while (4c) showed GI50 value 0.34 and 0.96 μM against HOP-92 and EKVX (Non-Small Cell Lung Cancer cell line) and 1.08 μM against MDA-MB-231/ATCC(Breast Cancer cell Line). In addition, molecular docking studies of the said MAGL inhibitors have also been presented in this article.

Introduction: Resveratrol and chalcones are lead compounds with good biological activities. Method: In this study, a series of novel derivatives (6-38) between resveratrol and chalcone possessing piperazine moiety have been synthesized, and in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and anti-proliferative effect on a panel of human tumor cell lines (Hela, A549 and SGC7901) by MTT assay were evaluated. Result: The results demonstrated that the substituents of the NH group of piperazine ring had an obvious influence on biological activities. Especially, compounds 13, 17, 30, 31 and 36 showed good inhibitory effect on the generation of NO compared to dexamethasone. Furthermore, analogs 20, 21, 22 and 25 were found to be the better anti-proliferative effect on 3 human tumor cell lines, which were found to be a better cytotoxic activity to positive control 5-FU. Many compounds displayed low cytotoxic effect on normal cells L02. Conclusion: Further FACs analysis showed that compounds 20 and 25 significantly induced apoptosis in A549 cell. These derivatives were considered as the potential anti-inflammatory and anti-tumor agents.

Background: A novel series of fused imidazole was prepared from the reaction of 2- bromoacetyl-3-phenyl-1,3,4-thiadiazole with various heterocyclic amines under microwave irradiation. The structures of all the novel products were elucidated based on the elemental analysis and spectral data. Results: In addition, the biological activity of the newly synthesized compounds was evaluated and the results obtained indicate their potency as anti-inflammatory, analgesic and anti- ulcer agents. Conclusion: The binding mechanism of the most active compounds was studied using MOE to analyze the molecular interactions.