Edotecarin

Edotecarin is an indolocarbazole class antitumor agent that has significant anticancer effects against various types of cancer, especially lung, breast, and stomach cancer.The conformation anal. of the edotecarin was performed using the PM3 method and six stable conformations were obtained.Afterwards the obtained lowest energy conformation was optimized at the DFT/B3LYP/6-31++G(d,p) level of theory.The vibrational wavenumbers, the HOMO, the LUMO and mol. electrostatic potential of the most stable conformer of edotecarin were calculated at the DFT/B3LYP/6-31++G(d,p) level of theory.The mol. docking of the edotecarin mol. against DNA, Topoisomerase I, DNA-Topoisomerase I complex,α5β1 and αIIbβ3 integrins were performed to reveal its binding modes and binding affinities.

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound zinc metallopeptidase that generates the vasodilatory peptide angiotensin 1-7 and thus performs a protective role in heart disease. It is considered an important therapeutic target in controlling the COVID-19 outbreak, since SARS-CoV-2 enters permissive cells via an ACE2-mediated mechanism. The present in silico study attempted to repurpose existing drugs for use as prospective viral-entry inhibitors targeting human ACE2. Initially, a clinically approved drug library of 7,173 ligands was screened against the receptor using molecular docking, followed by energy minimization and rescoring of docked ligands. Finally, potential binders were inspected to ensure molecules with different scaffolds were engaged in favorable contacts with both the metal cofactor and the critical residues lining the receptor's active site. The results of the calculations suggest that lividomycin, burixafor, quisinostat, fluprofylline, pemetrexed, spirofylline, edotecarin, and diniprofylline emerge as promising repositionable drug candidates for stabilizing the closed (substrate/inhibitor-bound) conformation of ACE2, thereby shifting the relative positions of the receptor's critical exterior residues recognized by SARS-CoV-2. This study is among the rare ones in the relevant scientific literature to search for potential ACE2 inhibitors. In practical terms, the drugs, unmodified as they are, may be introduced into the therapeutic armamentarium of the ongoing fight against COVID-19 now, or their scaffolds may serve as rich skeletons for designing novel ACE2 inhibitors in the near future.