Author: Richa, Kikoleho ; Imkongyanger ; Rudithongru, Lemzila ; Nakro, Vevosa ; Sinha, Upasana Bora ; Jamir, Latonglila ; Pankaj, Pranay Punj ; Ao, Ketiyala ; Namsa, Nima D ; Lotha, Tsenbeni N ; Ritse, Vimha

Background::Type 2 Diabetes Mellitus (T2DM) represents a significant and pressing worldwide health concern, necessitating the quest for enhanced antidiabetic pharmaceuticals. Guanidine derivatives, notably metformin and buformin, have emerged as pivotal therapeutic agents for T2DM management. Aims: The present study introduces an efficient one-pot synthesis method for the production of symmetrical guanidine compounds.Methods::This synthesis involves the reaction of isothiocyanates with secondary amines, employing an environmentally friendly and recyclable reagent, tetrabutylphosphonium tribromide (TBPTB).Results::A comprehensive assessment of the biological activity of the synthesized guanidine compounds, specifically in the context of T2DM, has been rigorously conducted.Conclusion::Additionally, computational analyses have unveiled their substantial potential as promising antidiabetic agents. Results highlight the relevance of these compounds in the ongoing pursuit of novel therapeutic solutions for T2DM.

01 Feb 2024·iScience

Insights into the action of the pharmaceutical metformin: Targeted inhibition of the gut microbial enzyme agmatinase

Article

Author: Wackett, Lawrence P ; Tassoulas, Lambros J

Metformin is the first-line treatment for type 2 diabetes, yet its mechanism of action is not fully understood. Recent studies suggest metformin's interactions with gut microbiota are responsible for exerting therapeutic effects. In this study, we report that metformin targets the gut microbial enzyme agmatinase, as a competitive inhibitor, which may impair gut agmatine catabolism. The metformin inhibition constant (K_i) of E. coli agmatinase is 1 mM and relevant in the gut where the drug concentration is 1-10 mM. Metformin analogs phenformin, buformin, and galegine are even more potent inhibitors of E. coli agmatinase (K_i = 0.6, 0.1, and 0.007 mM, respectively) suggesting a shared mechanism. Agmatine is a known effector of human host metabolism and has been reported to augment metformin's therapeutic effects for type 2 diabetes. This gut-derived inhibition mechanism gives new insights on metformin's action in the gut and may lead to significant discoveries in improving metformin therapy.

01 Jul 2023·Current Medicinal Chemistry

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

Article

Author: de Lima Barbosa, Helena Cristina ; Kawano, Daniel Fábio ; de Oliveira Neto, Xisto Antonio ; Fiori-Duarte, Ana Thereza ; Barssotti, Leticia

Abstract: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 the 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 in the diabetes, such as pancreas-protective, antioxidant, and anti-inflammatory activities. In this manuscript, 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 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 the wide range of molecular targets, as well as the multiple activities displayed by metformin, make this drug a promising prototype for the development of novel entities, particularly for the treatment of type 2 diabetes mellitus.

100 Deals associated with Buformin Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
-	Buformin Hydrochloride	A10BA03	DB04830

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Indication	Country/Location	Organization	Date
Diabetes Mellitus	JP	Nichi-Iko Pharmaceutical Co., Ltd.	21 Jul 2006

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrial Carcinoma	Preclinical	CN	University of North Carolina at Chapel Hill /Gene Mfg Ops/	01 Oct 2014

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