Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect

Abstract

Combating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced. Sulfonylurea category of anti diabetic drug often suffers from cross reactivity with sulfamethoxazole (SMX), a common drug in use to treat a handful of microbial infections. However the specific cellular target generating postprandial hypoglycemia on SMX administration is till date unraveled. The present work has been initiated to elucidate the effects of a group of sulfonamide drugs inclusive of SMX for their amylase inhibitory role. SMX inhibits porcine pancreatic amylase (PPA) in a noncompetitive mode with an average IC50 value 0.94 mM respectively. Interaction of SMX with PPA is manifested with gradual quenching of tryptophan fluorescence with concomitant shift in lambda max value (λmax). Binding is governed by entropy driven factor (24.8 cal mol(-1) K(-1)) with unfavorable contribution from enthalpy change. SMX interferes with the activity of acarbose in a synergistic mode to reduce the effective dose of acarbose as evident from the in vitro PPA inhibition study. In summary, loss of PPA activity in presence of SMX is indicative of structural changes of PPA which is further augmented in the presence of acarbose as explained in the schematic model and docking study.

α-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives

“…World Health Organization (WHO) declared this worldwide health problem as an epidemic disease to be the only noninfectious disease with such categorization 2 . This deadly disease is associated with numerous side effects such as impairment of functions of kidneys, heart, eye and nervous system affecting carbohydrate, protein and fat metabolism 3 . The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability 4 .…”

“…α-Glucosidase (α-Gls) inhibitors postpone digestion and absorption of intestinal carbohydrate 3 , 4 . They are agents convenient for the reduction of postprandial hyperglycemia by suppressing the absorption of glucose, hence being effective in the treatment of T2 diabetes and obesity.…”

Mitochondrial Impairment by Cyanine-Based Small Molecules Induces Apoptosis in Cancer Cells

“…Compounds 7n and 7p are structurally similar to obatoclax, which binds with the BH3 domain of Bcl-2 proteins . Hence, we carried out molecular docking studies using Auto Dock Vina in conjunction with MGL, ADT, and PMV software to quantify the binding affinity. , From these docking studies, the binding affinities of 7n and 7p in the BH3 domain of Bcl-2 were found to be −12 and −12.4 kcal/mol, respectively. These binding affinities were higher than the binding affinity of obatoclax (−6.5 kcal/mol) (Table S4).…”