Bioisosterism: an approach to develop new anti-cancer agents

Bioisosterism is a powerful strategy to develop novel drug molecules. This approach allows researchers to rationally design a drug molecule by replacing functional groups or atoms on a molecular scaffold with similar electronic or structural moieties to fine tune its biological activity. Thus, change in the structural properties enhances pharmacological properties such as selectivity, its binding affinity, metabolic stability and pharmacokinetics with minimized toxicity. In cancers, especially those that develop drug resistance become tolerant to most of the chemotherapeutics and targeted medications which is a bottle neck in the treatment. Thereby altering the existing pharmacophoric features of the molecule with its bioisosters can help in enhancing the selectivity, reducing the resistance and toxicity. In this review, we were mainly focused on collecting and compiling various classical and non-classical bioisosteric replacement strategies being considered to develop a new anticancer agent. Here we also emphasize and discuss some biological pathways that could be further utilized to understand the biology of the disease and to design and optimize a lead candidate. Overall, this review will be helpful for those researchers who are continuously involved in optimizing the existing molecules or drugs to develop next-generation therapeutics for cancer treatment.