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A new series of 20 benzofuran based sulphonamides was synthesized from salicylaldehyde and ortho-vanillin. Synthesized compounds (VIIIa–VIIIt) were characterized using FT-IR (Fourier-transform infrared spectroscopy), 1H-NMR (Proton nuclear magnetic resonance) and Mass spectroscopic studies. All 20 compounds were subjected to in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strains. Compounds (VIIIj), (VIIIi), (VIIIo) and (VIIId) were found to exhibit lower MICs (the minimum inhibitory concentrations) as 13, 18, 17 and 19 µg/mL respectively. To predict plausible modes of binding of these compounds, we carried out molecular docking analysis against a target type III polyketide synthase PKS18 from M. tuberculosis (PDB ID: 1TED). [ABSTRACT FROM AUTHOR]

A series of polysubstituted imidazoles were synthesized in good yields by employing stable and active silica-OSO3H catalyst via a one-pot four-component approach. This new protocol has the advantages of inexpensive, nontoxic, and heterogeneous catalyst along with mild reaction conditions, short reaction times, and easy workup and purification procedures, which enhance its practicality. The synthesized imidazoles were subjected to molecular docking with some bacterial target enzymes (PDB IDs: 1KZN, 1BAG, 1D7U, 2XCT). Compounds 1k, 1e, 1o, and 1i showed the best docking scores on selected targets, –8.2, –8.4, –8.5, and –9.3 kcal/mol, respectively. Antibacterial evaluation of the synthesized compounds against S. aureus, B. subtilis, E. coli, and K. pneumoniae revealed their potential activity with MIC values of 64 to 100 µg/mL. Imidazoles containing another heterocyclic unit such as pyridyl or thienyl (1d, 1f, 1h, and 1m) showed better antibacterial activity than other analogues. [ABSTRACT FROM AUTHOR]

A new series of benzofuran derivatives have been synthesized by the reaction of substituted N-(4-aminophenyl)-1-benzofuran-2-carboxamide with substituted aromatic sulfonyl chlorides in the presence of base with a suitable solvent at 30–100°C temperature and further characterized by Fourier-transform infrared spectroscopy (FT-IR), Proton nuclear magnetic resonance (1H-NMR), elemental analysis and mass spectroscopy studies. All the 26 newly synthesized compounds (Xa–z) were tested for their in-vitro antitubercular (anti-TB) activity against Mycobacterium tuberculosis H37Rv strains. Benzofuran based sulfamides (Xa) and (Xu) were found more potent with the minimum inhibitory concentration (MIC) values 64 µg/mL of each against M. tuberculosis H37Rv; which were then supported by molecular docking studies to gain more insights on the mode of inhibition of M. tuberculosis Polyketide synthase. [ABSTRACT FROM AUTHOR]

Objective: The tandem Knoevenagel-cyclocondensation reaction of aromatic aldehydes, malonitrile, and phenylhydrazine in water and ethanol at room temperature is described as an effective, one-pot, threecomponent synthesis of many scientifically relevant heterocyclic compounds. Methods: As a part of our efforts, we have synthesized pyrazole-4-carbonitriles and characterized using various spectroscopic methods and subjected for antimicrobial analysis. Results and Discussion: From our analysis, we observed best in vitro candidate as 5-amino-3-(2,5-difluorophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile. The molecular docking analysis on common bacterial target suggested the involvement of 2,2-dialkylglycine decarboxylase (PDB ID: 1D7U) as a target for compound (IVi) (docking score: –9.32 kcal/mol). Furthermore, a molecular dynamic simulation of 100 ns resulted in the stability of best docked candidate, (IVi): 1D7U. Conclusions: We propose that best docked candidate, (IVi) as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]

A new design of thiazolidin-4-one derivatives were evaluated for their cytotoxicity on CHO (Chinese Hamster ovary cells), SKOV3 (Human Ovarian cancer) and HeLa (Human cervical) cancer cell lines. All these compounds exhibited moderate cytotoxicity against CHO cells but showed potent anticancer activity against both SKOV3 and HeLa cell lines. A high antiproliferative activity of compound (Va), (Vd) and (Vm) against SKOV3 and (Va), (Vm) and (Vq) against HeLa cell lines were observed. It is interesting to note that (Vq) and (Vc) are comparatively lesser toxic to the normal CHO cells but highly cytotoxic against HeLa and SKOV3 cells. In the antimicrobial activity (Vb), (Vc) and (Vq) compounds displayed a moderately antifungal activity against Aspergillus niger and A. flavus at 150 μg/mL concentration. Moreover, molecular docking and molecular dynamics analysis over 100 ns with target FGFR2 (4j96): (Vq) retained good acceptable profiles for stability of this complex. Based on these bioactivity studies, it is indicated that (Vb) and (Vq) compounds can be potential substitutes for the treatment of ovarian and cervical cancer respectively because of their high specificity to both types of ovarian and cervical cancers with minimal toxicity to normal cells. [ABSTRACT FROM AUTHOR]

Cancer is a major public health problem in the United States and many other parts of the world. 4-thiazolidinone scaffold is an important group of heterocycles. A new series of 2-Imino-4-thiazolidinone derivatives were synthesized and tested for their cytotoxic activity against four cancer cell lines U937, THP-1, Colo205 and B16F10. From the results it was concluded that some of the compounds are found to be more active on U937 cell lines than the positive control anticancer drug, Etoposide. Our results indicate that all the test compounds (100%, IVa–s) are active against U937 cells. In order to investigate further structural aspects, these compounds were subjected to molecular modeling studies. 2D-QSAR analysis (with robust, r2 = 0.83, q2 = 0.74 and pred_r2 = 0.80) suggests that the substitution of groups on tertiary carbon atom and groups containing lesser dipole moment on thiazolidinone core moiety could be beneficial for improving activity. Apart from this, 3D-QSAR analysis with 5 featured common pharmacophore hypothesis (AAAAR) also suggests the importance of hydrophobic substitution at R3, R4, R5 positions on the phenyl ring connected to thiazolidinone core moiety for improving cytotoxic potency. [ABSTRACT FROM AUTHOR]

Aims: To study anti-ulcer effect of Amlodipine and compared it with ranitidine in indomethacin, alcohol and pyloric ligation-induced gastric ulcers in wistar rats. Materials and Methods: Gastric ulcers were induced in Wistar albino rats by oral administration of indomethacin (200 mg/kg), alcohol (80%, 1 ml/100 gm) and by pyloric ligation. Antiulcer activity of amlodipine (0.5 mg/kg, i.p.) was observed either alone or in combination with ranitidine (15 mg/kg, i.p.), on ulcer index, gastric pH and gastric volume. Statistical analysis was done by ANOVA and unpaired one tailed 't' test. P<0.05 was considered statistically significant. Results: Amlodipine produced significant (P<0.05) decrease in ulcer index and gastric pH as compared to control. It also produced significant (P<0.05) increase in gastric volume as compared to ranitidine. The anti-ulcer effects of ranitidine were significantly higher than that of amlodipine. Combination of amlodipine and ranitidine did not show significant increase in anti-ulcer activity as compared with ranitidine alone. Conclusions: Amlodipine produced significant anti-ulcer effects in all 3 experimental models. Amlodipine increased the volume of gastric secretions as compared to ranitidine. [ABSTRACT FROM AUTHOR]