Synthesis of sulpha drug based hydroxytriazene derivatives: Anti-diabetic, antioxidant, anti-inflammatory activity and their molecular docking studies.

Autor: Sharma P; Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan, India., Dayma V; Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan, India., Dwivedi A; Department of Environmental Sciences, Mahatma Gandhi Chitrakoot Vishwvidhyalay, Chitrakoot, Satna, Madhya Pradesh, India., Baroliya PK; Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan, India. Electronic address: prabhatkbaroliya@mlsu.ac.in., Tripathi IP; Department of Environmental Sciences, Mahatma Gandhi Chitrakoot Vishwvidhyalay, Chitrakoot, Satna, Madhya Pradesh, India., Vanangamudi M; Department of Medicinal and Pharmaceutical Chemistry, Sree Vidyanikethan College of Pharmacy, Tirupathi, Andhra Pradesh, India., Chauhan RS; Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan, India., Goswami AK; Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan, India. Electronic address: akumargoswami56@gmail.com.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 Mar; Vol. 96, pp. 103642. Date of Electronic Publication: 2020 Jan 31.
DOI: 10.1016/j.bioorg.2020.103642
Abstrakt: Herein, we report synthesis, characterization, anti-diabetic, anti-inflammatory and anti-oxidant activities of hydroxytriazenes derived from sulpha drugs, namely sulphanilamide, sulphadiazine, sulphapyridine and sulphamethazine. Before biological screening of the compounds, theoretical prediction using PASS was done which indicates probable activities ranging from Pa (probable activity) values 65-98% for anti-inflammatory activity. As per the predication, experimental validation of some of the predicted activities particularly anti-diabetic, anti-inflammatory and anti-oxidant was done. Anti-diabetic activities have been screened using two methods namely α-amylase and α-glucosidase inhibition method and IC 50 values were ranging from 66 to 260 and 148 to 401 µg/mL, while for standard drug acarbose the values were 12 µg/mL and 70 µg/mL, respectively. Docking studies have also been done for antidiabetic target pancreatic alpha amylase. The molecular docking studies in α-amylase enzyme reveal that the middle phenyl ring of all the compounds mainly occupies in the small hydrophobic pocket formed by the Ala198, Trp58, Leu162, Leu165 and Ile235 residues and sulphonamide moiety establish H-bond interaction by two water molecules. Further, anti-inflammatory activity has been evaluated using carrageenan induced paw-edema method and results indicate excellent anti-inflammatory activity by hydroxytriazenes (71 to 97%) and standard drug diclofenac 94% after 4 h of treatment. Moreover, antioxidant effect of the compounds was tested using DPPH and ABTS methods. All the compounds displayed good results (24-488 µg/mL) against ABTS radical and many compounds are more active than ascorbic acid (69 µg/mL) while all other compounds showed moderate activity against DPPH radical (292-774 µg/mL) and ascorbic acid (29 µg/mL). Thus, the studies reveal potential of sulfa drug based hydroxytriazenes as candidates for antidiabetic, anti-inflammatory and antioxidant activities which have been experimentally validated.
Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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