BIOACTIVE CHEMICAL NUCLEI AS PROMISING SCAFFOLDS FOR ANTICANCER DRUG DEVELOPMENT

Abstract

Given the prevalence of unchecked cellular growth, genetic instability, metastasis, therapeutic resistance, and treatment-associated toxicity, cancer continues to be one of the biggest threats to world health. While targeted therapy, immunotherapy, conventional chemotherapy, and other multimodal techniques have significantly improved cancer management, therapeutic outcomes are still limited by tumor heterogeneity, drug resistance, side effects, and poor selectivity. In this regard, privileged heterocyclic scaffolds and bioactive chemical nuclei have become significant structural frameworks for the identification and improvement of new anticancer drugs. They can interact with a variety of cancer-associated targets and enable systematic structure–activity relationship (SAR) optimization thanks to their advantageous electronic, steric, hydrogen-bonding, and molecular-recognition features. The structural traits, primary anticancer processes, molecular targets, and significant SAR aspects of a few heterocyclic bioactive scaffolds—benzimidazole, quinazoline, pyrimidine, indole, and triazole/pyrazole are highlighted in this review. The successful conversion of these scaffolds into FDA approved, clinically effective anticancer medications is highlighted, highlighting their importance in contemporary medicinal chemistry. Recent developments in scaffold-based anticancer drug discovery, such as molecular hybridization, multitarget drug design, structure-based drug design. These new methods offer chances to enhance pharmacokinetic and pharmacodynamic characteristics, overcome medication resistance, and increase target selectivity. There are still issues with toxicity, resistance, tumor heterogeneity, drug-like characteristics, and clinical translation despite significant advancements. Therefore, the integration of bioactive scaffold optimization with precision oncology, computational technologies, biomarker-guided design, and novel target-modulation techniques will be necessary for future anticancer drug discovery. All things considered, bioactive heterocyclic nuclei remain flexible and clinically proven platforms for the creation of novel anticancer treatments.