Antibacterial evaluation and molecular docking studies of pyrazole-thiosemicarbazones and their pyrazole-thiazolidinone conjugates.

A library of pyrazole-thiazolidinone conjugates was synthesized using a molecular hybridization approach through a Vilsmeier-Haack reaction. The compounds were tested for anti-microbial activity against two Gram-positive bacteria (Staphylococcus aureus and methicillin-resistant Staphylococcus aureus) and four Gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa). Among the compounds tested, 3-((2,4-dichlorophenyl)-1-(2,4-dinitrophenyl)-1H-pyrazol-yl)methylene)hydrazinecarbothioamide (3a) and 2-((3-(2-chlorophenyl)-1-(2,4 dinitrophenyl)-1H-pyrazol-4-yl)methyleneamino)thiazolidin-4-one (4b) emerged as the most potent anti-microbial compounds with minimum bactericidal concentrations of < 0.

Triarylethylene-indolin-2,3-dione molecular conjugates: design, synthesis, docking studies and anti-proliferation evaluation.

A series of 1-1,2,3-triazole-linked ospemifene-isatin and -methylated ospemifene-isatin conjugates were synthesized and assayed for their anti-proliferative activities against estrogen-responsive as well as estrogen-non-responsive cells. The non-cytotoxic conjugate 14e, with an optimal combination of bromo substituents at the C-5/C-7 positions of isatin, proved to be a promising hit with an IC value of 31.62 μM against MCF-7 and 19.

Synthesis, Cytotoxicity and Antimicrobial Evaluation of New Coumarin-Tagged β-Lactam Triazole Hybrid.

A series of coumarin-tagged β-lactam triazole hybrids (10a-10o) were synthesized and tested for their cytotoxic activity against MDA-MB-231 (triple negative breast cancer), MCF-7 (estrogen receptor positive breast cancer (ER+)) and A549 (human lung carcinoma) cancer cell lines including one normal cell line, HEK-293 (human embryonic kidney). Two compounds 10b and 10d exhibited substantial cytotoxic effect against MCF-7 cancer cell lines with IC values of 53.55 and 58.

Diastereoselective approach to rationally design tetrahydro-β-carboline-isatin conjugates as potential SERMs against breast cancer.

A series of tetrahydro-β-carboline-isatin conjugates, with varying substituents as well as stereochemistry at C-1 and C-5 position of tetrahydro-β-carboline (THβC) and isatin ring, were prepared and assayed for anti-proliferative efficacy on Estrogen Responsive ER(+) (MCF-7) and ER(-ve) MDA-MB-231 cell-lines. The synthesized scaffolds displayed selective anti-proliferative efficacy against MCF-7 cell-line with the most active conjugate 8b exhibiting an IC value of 37.42 μM, comparable to that of peganumine A, a tetrahydro-β-carboline analogue, isolated from .

ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.

Despite new agent development and short-term benefits in patients with colorectal cancer (CRC), metastatic CRC cure rates have not improved due to high rates of 5-fluorouracil (5-FU)/leucovorin/oxaliplatin (FOLFOX)-resistance and a clinical therapeutic plateau. At the same time, this treatment regime leads to significant toxicity, cost, and patient inconvenience. Drug-resistance is linked to CRC stem cells, which are associated with the epidermal-to-mesenchymal transition (EMT) pathway.

Synthesis, computational studies and antiproliferative activities of coumarin-tagged 1,3,4-oxadiazole conjugates against MDA-MB-231 and MCF-7 human breast cancer cells.

A novel library of coumarin tagged 1,3,4 oxadiazole conjugates was synthesized and evaluated for their antiproliferative activities against MDA-MB-231 and MCF-7 breast cancer cell lines. The evaluation studies revealed that compound 9d was the most potent molecule with an IC value of <5 µM against the MCF-7 cell line. Interestingly, compounds 10b and 11a showed a similar trend with lower inhibitory concentration (IC = 7.

1-1,2,3-Triazole Tethered Nitroimidazole-Isatin Conjugates: Synthesis, Docking, and Anti-Proliferative Evaluation against Breast Cancer.

1-1,2,3-Triazole tethered imidazole-isatin and imidazole-isatin-thiosemicarbazone conjugates were synthesized and evaluated against MCF-7 and MDA-MB-231 cell lines. Antiproliferative activities of the synthesized conjugates revealed an optimum combination of longer alkyl chain length as spacer and a halogen-substituent on the isatin ring as a pre-requisite for good activity. The compound with an optimum combination of chloro-substituent at C-5 position of isatin ring and a butyl chain length proved to be most active and noncytotoxic with IC of 54.

Current anti-diabetic agents and their molecular targets: A review.

Diabetes mellitus is a medical condition characterized by the body's loss of control over blood sugar. The frequency of diagnosed cases and consequential increases in medical costs makes it a rapidly growing chronic disease that threatens human health worldwide. In addition, its unnerving statistical projections are perilous to both the economy of the nation and man's life expectancy.

Pharmacophore-Based 3D-QSAR Analysis of Thienyl Chalcones as a New Class of Human MAO-B Inhibitors: Investigation of Combined Quantum Chemical and Molecular Dynamics Approach.

Selective monoamine oxidase-B (MAO-B) inhibitors are imperative in the treatment of various neurodegenerative disorders. Herein, we describe the pharmacophore generation and atom-based three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses of previously reported thiophene-based hMAO-B inhibitors by our research group. The aim of this study was to identify the principal structural features that could potentially be responsible for the inhibitory activity of hMAO-B inhibitors.

Recent advancements in the development of anti-tuberculosis drugs.

Modern chemotherapy has significantly improved patient outcomes against drug-sensitive tuberculosis. However, the rapid emergence of drug-resistant tuberculosis, together with the bacterium's ability to persist and remain latent present a major public health challenge. To overcome this problem, research into novel anti-tuberculosis targets and drug candidates is thus of paramount importance.