Optimization of Dibromoverongiaquinol and Aeroplysinin-1 as anticancer and antimicrobial drug leads

Abstract

It is well known that preclinical pipeline continues to supply several hundreds of novel marine compounds every year and those continue to feed the clinical pipeline with potentially valuable compounds. Although newlinemarine product leads have historically been confronted with many obstacles, including sustainable and extreme cytotoxicity to the newlinenormal cell types despite having advantage of being effective at many fold less concentration than the standard drugs. Traditionally, among the first options to be explored for the supply of marine derived small molecules is chemical synthesis. Unfortunately, the structural complexity of marine molecules, which suggests novel mechanisms of action and high selectivity, has also resulted in few economically newlinefeasible strategies for total chemical synthesis. Another fairly laborintensive newlinestrategy is to do studies of the biological roles of marine natural product pharmacophores with a clearly defined structural moiety, and attempt to define whether the critical pharmacophore via newlinesynthesis, chemical degradation, modification, or a combination of newlinethese, can result in more practical drugs based on a marine prototype. In the past several decades, there have been numerous drug discovery studies defining anticancer and antimicrobial molecular targets which newlinesubsequently have been validated by innumerable natural and synthetic compounds with the adaptation of the expensive and time consuming wet lab studies. Advancement in the bioinformatics tools and software enables the easy screening of multiple compounds against multiple targets, if a well validated and elucidated in-silico pathway has been newlineestablished.