Entering the Sugar Rush Era: Revisiting the Antihyperglycemic Activities of Biguanides after a Century of Metformin Discovery.

Autor:	de Oliveira Neto XA; Faculty of Pharmaceutical Sciences, University of Campinas - UNICAMP, 13083-871 Campinas-SP, Brazil.; Institute of Chemistry, University of Campinas - UNICAMP, 13083-970 Campinas-SP, Brazil., Barssotti L; Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas-UNICAMP, 13083-864 Campinas-SP, Brazil., Fiori-Duarte AT; Faculty of Pharmaceutical Sciences, University of Campinas - UNICAMP, 13083-871 Campinas-SP, Brazil.; Institute of Chemistry, University of Campinas - UNICAMP, 13083-970 Campinas-SP, Brazil., de Lima Barbosa HC; Obesity and Comorbidities Research Center, Institute of Biology, University of Campinas-UNICAMP, 13083-864 Campinas-SP, Brazil., Kawano DF; Faculty of Pharmaceutical Sciences, University of Campinas - UNICAMP, 13083-871 Campinas-SP, Brazil.; Institute of Chemistry, University of Campinas - UNICAMP, 13083-970 Campinas-SP, Brazil.
Jazyk:	angličtina
Zdroj:	Current medicinal chemistry [Curr Med Chem] 2023; Vol. 30 (22), pp. 2542-2561.
DOI:	10.2174/0929867329666220820151959
Abstrakt:	The development of clinically viable metformin analogs is a challenge largely to be overcome. Despite being an extremely efficient drug for the treatment of type 2 diabetes mellitus, multiple studies were conducted seeking to improve its hypoglycemic activity or to ameliorate aspects such as low oral absorption and the incidence of gastrointestinal side effects. Furthermore, efforts have been made to attribute new activities, or even to expand the pre-existing ones, that could enhance its effects on diabetes, such as pancreas-protective, antioxidant, and anti-inflammatory activities. In this paper, we describe the analogs of metformin developed in the last three decades, highlighting the lack of computationally based rational approaches to guide their development. We also discuss this is probably a consequence of how unclear the mechanism of action of the parent drug is and highlight the recent advances towards the establishment of the main molecular target(s) for metformin. We also explored the binding of metformin, buformin and phenformin to the mitochondrial respiratory chain complex I through molecular docking analyses and reviewed the prospects of applying computational tools to improve the success in the development of such analogs. Therefore, it becomes evident that the wide range of molecular targets and the multiple activities displayed by metformin make this drug a promising prototype for developing novel entities, particularly for treating type 2 diabetes mellitus. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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