e-space
Manchester Metropolitan University's Research Repository

Bis-coumarins; non-cytotoxic selective urease inhibitors and antiglycation agents

Salar, U and Nizamani, A and Arshad, F and Khan, KM and Fakhri, MI and Perveen, S and Ahmed, N and Choudhary, MI (2019) Bis-coumarins; non-cytotoxic selective urease inhibitors and antiglycation agents. Bioorganic Chemistry, 91. ISSN 0045-2068

[img]
Restricted to Repository staff only until 31 July 2021.
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB)

Abstract

© 2019 Elsevier Inc. The current study is concerned with the identification of lead molecules based on the bis-coumarin scaffold having selective urease inhibitory and antiglycation activities. For that purpose, bis-coumarins (1-44) were synthesized and structurally characterized by different spectroscopic techniques. Eight derivatives 4, 8-10, 14, 17, 34, and 40 demonstrated urease inhibition in the range of IC50 = 4.4 ± 0.21–115.6 ± 2.13 μM, as compared to standard thiourea (IC50 = 21.3 ± 1.3 μM). Especially, compound 17 (IC50 = 4.4 ± 0.21 μM) was found to be five-fold more potent than the standard. Kinetic studies were also performed on compound 17 in order to identify the mechanism of inhibition. Kinetic studies revealed that compound 17 is a competitive inhibitor. Antiglycation activity was evaluated using glycation of bovine serum albumin by methylglyoxal in vitro. Compounds 2, 11-13, 16, 17, 19–22, 35, 37, and 42 showed good to moderate antiglycation activities with IC50 values of 333.63–919.72 μM, as compared to the standard rutin (IC50 = 294.46 ± 1.5 μM). Results of both assays showed that the compounds with urease inhibitory activity did not show any antiglycation potential, and vice versa. Only compound 17 showed dual inhibition potential. All compounds were also evaluated for cytotoxicity. Compounds 17, 19, and 37 showed a weak toxicity towards 3 T3 mouse fibroblast cell line. All other compounds were found to be non-cytotoxic. Urease inhibition is an approach to treat infections caused by ureolytic bacteria whereas inhibition of glycation of proteins is a strategy to avoid late diabetic complications. Therefore, these compounds may serve as leads for further research.

Impact and Reach

Statistics

Downloads
Activity Overview
0Downloads
34Hits

Additional statistics for this dataset are available via IRStats2.

Altmetric

Actions (login required)

View Item View Item