Design, synthesis, and cytotoxicity of ibuprofen-appended benzoxazole analogues against human breast adenocarcinoma.

A library of novel ibuprofen-appended benzoxazole analogues (7a-l) was synthesized via a series of nitration, reduction, and condensation-cyclization reactions and screened for their in vitro anticancer activity against human breast cancer MCF-7 and MDA-MB-231 cell lines using doxorubicin as a standard reference. Compounds 7h and 7j displayed outstanding activity against the MCF-7 cell line with an IC50 value of 8.92 ± 0.91 µM and 9.14 ± 8.22 µM, respectively, compared to the doxorubicin IC50 value of 9.29 ± 1.02 µM. Compound 7h also exhibited outstanding activity against the MDA-MB-231 cell line with an IC50 value of 7.54 ± 0.95 µM compared to the doxorubicin IC50 value of 7.68 ± 5.36 µM. Compounds 7h, 7i, 7j, and 7g showed identical morphological changes to those showed by doxorubicin. The molecular docking study against ERα unveiled their best docking scores and binding interactions in agreement to experimental results. Pharmacokinetics prediction envisaged their drug-like properties suitable for therapeutic applications.

Synthesis, antimicrobial and antioxidant activity of triazole, pyrazole containing thiazole derivatives and molecular docking studies on COVID-19.

New series of biologically active triazole and pyrazole compounds containing 2, 4-disubstituted thiazole analogues (12a-l) were synthesized from p-hydroxy benzaldehyde and phenyl hydrazine in excellent yields and purity. All the synthesized compounds were unambiguously identified based on their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS). The final derivatives were evaluated for their in vitro anti-microbial activity after thorough purification. Among all the tested compounds, the compound 12e, 12f and 12 k possess the highest growth inhibitory activity at MIC values of 4.8, 5.1 and 4.0 µg/ml respectively. The antioxidant properties of these compounds demonstrated and revealed remarkable activity compared to the standard antioxidant by using the DPPH free radical-scavenging assay. Moreover, molecular docking studies to evaluate the probable interactions with the catalytic domain of the gram-positive S. aureus topoisomerase IV enzyme may provide new insights for developing these new hybrids as potential antimicrobial agents. The binding affinities of compounds 12a-l were ranging from - 10.0 to - 11.0 kcal/mol with topoisomerase IV enzyme and with COVID-19 main protease binding affinities are ranging from - 8.2 to - 9.3 kcal/mol. These docking studies reveal that the compounds 12a-l could be the best inhibitors for the novel SARS Cov-2 virus and have more future in discovery of potent drug candidates.

Synthesis of fused bis-indazoles/indazoles via a one-pot sequential strategy.

We report here an efficient synthesis of fused bis-indazoles/indazoles via a one-pot sequential strategy starting from o-azido aldehydes and amines. This novel method involves the sequential formation of 2H-indazole followed by a Pd-catalyzed intramolecular cross-dehydrogenative coupling reaction. Overall, this one-pot sequential reaction involved the formation of new five bonds, resulting in the formation of three heterocyclic rings.