Studies in Natural Product Chemistry, Volume 73 - Chapter 11: Marine-derived antidiabetic compounds: an insight into their sources, chemistry, SAR, and molecular mechanisms

Elsevier, Studies in Natural Products Chemistry, Volume 73, 2022, pp 467-504
Pathak K., Gogoi U., Saikia R., Pathak M.P., Das A.

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.