Design and development of new inhibitors against breast cancer, Monkeypox and Marburg virus by modification of natural Fisetin via in silico and SAR studies

Abstract

The natural Fisetin and its derivatives have been shown to have effective bioactivity and strong pharmacological profile, which is continuously drawing the interest of therapeutic applications to the development of new biomolecules against Breast cancer and Monkeypox, and Marburg viral infection, while computational approaches and the study of their structure-activity relationship (SAR) are the most eloquent and reliable platform for performing their hypothetical profile renovation. So, the main perspective of this investigation is to evaluate dual function of Fisetin and its derivatives against both virus and cancerous target. First and foremost, the prediction of activity spectra for materials (PASS) valuation has provided preliminary data on the antiviral, antibacterial, antiparasitic, and anticancer possibilities of the mentioned compounds. According to the evidence, PASS predicted scores were shown to perform better in antineoplastic and antiviral than antibacterial, and antiparasitic efficiency; as evidenced by their higher PASS scores in antineoplastic and antiviral drug tests. Breast cancer, Monkeypox, and Marburg virus have been selected as targeted pathogens, and different in silico studies were conducted to determine the dual function of mention derivatives. The “Lipinski five rules,” on the other hand, has been subjected to extensive testing for drug-like characteristics. Molecular docking against Breast cancer, Monkeypox, and Marburg virus have been accomplished after confirmation of their bioactivity. The molecular docking evaluation against targeted disease displayed re-markable binding affinity and non-bonding engagement, with most of the results indicating that derivatives are more effective than the FDA approved standard antiviral, and antineoplastic drugs. Finally, the ADMET characteristics have been computed, and they indicate that the substance is suitable to use and did not have any chance to produce adverse effects on aquatic or nonaquatic environment, as well as having a highly soluble capacity in water medium, high G.I absorption rate, with outstanding bioavailability index. Therefore, these mentioned Fisetin derivatives could be suggested as potential medication against Breast cancer and newly reported Monkeypox, and Marburg virus, and may further proceed for laboratory experiment, synthesis, and clinical trials to evaluate their practical value.