Background: There are many biomarkers associated with breast cancer. Higher expression of PIK3CA (Phosphoinositide 3-kinase Cα), in its upregulated form, is associated with Hr + and Her2 − breast cancer; therefore, many drugs were synthesized against this protein to treat breast cancer patients. FDA recently approved that the drug alpelisib also inhibits PI3KCα (PDB ID-5DXT) in BC patients with Hr + and Her2 −. In present study, we have exploited fourteen coumarin-carbonodithioate derivatives and alpelisib against this protein along with eighteen others which are responsible for causing BC through computational analysis. We have used Schrödinger Maestro 11.2 version for our in silico docking study, and to calculate relative binding energies of ligands, we used prime MM-GBSA module. Result: Docking study revealed that among all fourteen compounds, 2f, 2a, 2d, and 2e showed the highest G score than the alpelisib and coumarin against PI3KCα with − 9.3, − 9.0, − 9.0 and − 9.1 kcal/mol respectively, along with individual G score of alpelisib (− 8.9) and coumarin (− 7.9). Prime MM-GBSA analysis gave the relative binding energies of alpelisib, 2f, and 2e with − 19.94864535, − 18.63076296 and − 13.07341286 kcal/mol sequentially. Conclusion: This study provides an insight into the coumarin-carbonodithioate derivatives that could act as inhibitors of PI3KCα like alpelisib. Further prime MM-GBSA study revealed ligand binding energies and ligands strain energies.

Recently, heterogeneous catalysts have been explored eximiously in the synthesis of heterocyclic compounds. Therefore, here we used solid-supported heterogeneous silica sulfuric acid as a catalyst for the synthesis of Schiff's base of 3-chloroformylcoumarin in view of simplified procedure, reusability and acceptable efficiency, which are required in organic synthesis. An efficient and facile methodology is preferred for synthesis of a class of chromeno-3-substituted derivatives (1a–1l) with good yields. The molecular docking results showed excellent binding interactions with the Mycobacterium tuberculosis InhA-D148G mutant (PDB: 4DQU). The same biomolecules were screened for their in vitro anti-tubercular activity against the M.tb H37Rv strain and antimicrobial studies. Physico-chemistry, toxicity prediction with IC50 value and bioactivity score were also calculated for title compounds. Most active compounds were further tested for cytotoxicity studies and exhibited low-level cytotoxicity against Vero cells. The suggested conjugates are promising lead compounds for the subsequent investigation in search of new anti-tubercular agents. All the conjugates were obtained within the range and followed the Lipinski rule of 5, indicating more ‘drug-like’ nature.

No abstract

An approach to 2,4,5-substituted thiazoles containing coumarins were synthesized via Intramolecular Knoevenagel condensation-cyclization reaction using triethylamine (TEA) as a base and are confirmed by spectroscopic analysis. In-vitro screening, molecular docking (performed to preferred binding mode and supports the interaction of thiazole-coumarin derivatives with enzyme) studies are reported. A detailed study subsidized by theoretical calculations directed us to determine that: an intact thiazole and coumarin rings appear to be needful for a strong antifungal activity, dis similarly determined by the substituents on coumarin and change in nitrogen rings. All the derived conjugates are fungicide and enhancing their antifungal inhibition due to different substitutions. The presence of flexible connecting N-substitutions found to be required for antifungal inhibition, although its ring size shows reciprocally with antifungal nature in most fungi. Some active derivatives did not found effective inhibitor against bacterial strains, indicating that their inhibition is selective to pathogenic fungi and also they are non-toxic at MIC concentrations.[a] S.

No abstract