"SYNTHESIS AND STRUCTURAL MODIFICATION OF ALLIINDERIVATIVES FOR ENHANCED ANTICANCER ACTIVITY"

AbstractCancer remains a major global health concern and continues to be one of the leading causesof morbidity and mortality despite significant advances in diagnosis and treatment. Theincreasing incidence of drug resistance, severe adverse effects, and limited selectivityassociated with conventional chemotherapy has intensified the search for safer and moreeffective therapeutic agents. Natural products have long served as valuable sources ofbioactive molecules for anticancer drug discovery. Among these, alliin (S-allyl-L-cysteinesulfoxide), the principal sulfur-containing amino acid derivative found in Allium sativum(garlic), has attracted considerable scientific attention because of its antioxidant, antiinflammatory, antimicrobial, immunomodulatory, and anticancer properties. Recent researchhas demonstrated that alliin and its derivatives inhibit cancer cell proliferation throughmultiple mechanisms, including induction of apoptosis, regulation of oxidative stress,suppression of angiogenesis, inhibition of inflammatory signaling pathways, and modulationof cell-cycle progression. However, the therapeutic application of native alliin is restricted bypoor bioavailability, limited membrane permeability, moderate cytotoxic potency, and rapidmetabolic degradation. Structural modification has emerged as an effective medicinalchemistry strategy to overcome these limitations by improving physicochemical properties,metabolic stability, target specificity, and biological efficacy. This review summarizes thechemistry, biosynthesis, pharmacological activities, and anticancer mechanisms of alliin, withparticular emphasis on recent advances in the synthesis and structural optimization of alliinderivatives. Furthermore, current evidence regarding structure–activity relationships,molecular targets, nanotechnology-based drug delivery systems, and preclinicalinvestigations is critically discussed. The review also highlights the challenges associatedwith clinical translation and identifies future research directions for the development of alliinbased anticancer therapeutics. Overall, structurally modified alliin derivatives representpromising lead compounds for next-generation anticancer drug development and warrantfurther investigation through comprehensive preclinical and clinical studies.