Marine-derived antidiabetic compounds: an insight into their sources, chemistry, SAR, and molecular mechanisms
Kalyani Pathak, Urvashee Gogoi, Riya Saikia, Manash Pratim Pathak, Aparoop Das
Abstract
Type-2 diabetes (T2DM) is a chronic metabolic disease that can only be managed with a healthy lifestyle comprising diet, exercise, and proper medication. To manage T2DM, a person has to take anti-diabetic drugs for a long time which may result in adverse reactions as well as other associated complications. So, there is a search for antidiabetic drugs fromthemarine origin which are reported to be highly efficacious in T2DM. Although numerous new marine-derived metabolites and bioactive compounds are being reported to be anti-diabetic, a multi-level approach based analysis on molecular investigations at genomic, metagenomic , transcriptomic , metatranscriptomic, proteomic , and metabolomic levels is essential to discover these resources and further explore key molecular processes involved in their production and action. Due to thelack of proper literature on in-silico elucidation of promising marine compounds, either some of them show sub-therapeutic activity or some are reported to be cytotoxic in various in-vitro studies. Two compounds (7E)-9-oxohexadec-7-enoic acid and (10E)-9-oxohexadec-10-enoic acid from the marine algae Chaetoceros karianus were reported to be anti-diabetic however, further synthetic approach following SAR analysis exhibited dual Peroxisome proliferator-activated receptor (PPAR) α/γ agonist activity. Another marine drug candidate, compound 14n, is hypothesized to be a better interaction structure for binding to theProtein tyrosine phosphatase 1B (PTP1B) enzyme with stronger activity and better selectivity if the cyclohexane ring is further modified by adding a long alkyl chain and hydrogen bond donor. Two bromophenols, 2,4,6-tribromophenol and 2,4-dibromophenol, isolated and purified from the red alga Grateloupiaelliptica were found to possess high α -glucosidase inhibitory activity. It is possible that the degree of bromination in these molecules may have a strong relationship with their α-glucosidase inhibitory activity. This chapter deals with the current developments and upcoming challenges in the field of bioinformatics, chemical and molecular analysis of certain marine-derived bio-active compounds showing efficacy against T2DM.