S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4- oxadiazole-5-thiol derivatives. 2. Anti-bacterial, enzymeinhibitory and hemolytic activities

Kaniz Rubab,Sabahat Z Siddiqui,Sidra Hassan,Aziz-Ur- Rehman,Muhammad Shahid,Muhammad A Lodhi,Muhammad A Abbasi,Muhammad Ashraf,Ayesha Shaukat,Hina Fatima,Mehreen Ghufran,Irshad Ahmad

doi:10.4314/tjpr.v15i7.24

Abstract

Purpose : To evaluate the antibacterial, enzyme-inhibitory and hemolytic activities of Salkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol derivatives. Methods : Antibacterial activities of the compounds were evaluated using broth dilution method in 96 well plates. Enzyme inhibitory activities assays were investigated against α-glucosidase, butyrylcholinesterase (BchE) and lipoxygenase (LOX) using acarbose, eserine and baicalien as reference standards, respectively. A mixture of enzyme, test compound and the substrate was incubated and variation in absorbance noted before and after incubation. In tests for hemolytic activities, the compounds were incubated with red blood cells and variations in absorbance were used as indices their hemolytic activities. Results : The compounds were potent antibacterial agents. Five of them exhibited very good antibacterial potential similar to ciprofloxacin, and had minimum inhibitory concentrations (MIC) of at least 9.00 ± 4.12 μM against S. aureus, E.coli, and B. subtilis. One of the compounds had strong enzyme inhibitory potential against α-glucosidase, with IC50 of 17.11 ± 0.02 μg/mL which was better than that of standard acarbose (IC50 38.25 ± 0.12 μg/mL). Another compound had 1.5 % hemolytic activity. Conclusion : S-Alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol deviratives with valuable antibacterial, anti-enzymatic and hemolytic activities have been successfully synthesized. These compounds may be useful in the development of pharmaceutical products. Keywords : 2-(1H-Indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol derivatives, Enzyme inhibition, Antibacterial activity, Hemolytic activity, Molecular docking

Highlights

The synthesis and evaluation of 2, 5disubstituted-1,3,4-oxadiazole-2-thiol derivatives have received attention in the past decades
In vitro screening of the synthesized compounds against α-glucosidase, BChE and LOX revealed that these molecules exhibited variable inhibitory potential as shown by their IC50 values (Table-1)
Our results revealed that the 5-(1Hindol-3yl-methyl)-1,3,4-oxadiazole-2-thiol derivatives (6a-6u) had variable inhibitory potencies against α-glucosidase, BChE and LOX

Summary

Introduction

The synthesis and evaluation of 2, 5disubstituted-1,3,4-oxadiazole-2-thiol derivatives have received attention in the past decades. The medicinal values of these compounds are diverse, and include anti-edema and antiinflammatory, anti-microbial, analgesic, antimycobacterial, anti-convulsant, anti-tumor, antimalarial, anti-hepatitis B, anti-tuberculosis, insecticidal, anti-HIV and anti-Parkinsonism activities [1,2]. The ability of these compounds to inhibit certain enzymes such as cholinesterases, α-glucosidase and lipoxygenase can exploited for medicinal purposes. Cholinesterases are present in cholinergic and non-cholinergic tissues, as well as plasma and other body fluids [3,4,5]. Lipoxygenase are important enzymes in the biosynthesis of leukotrienes used for the treatment of inflammation and allergic diseases [7,8]. In continuation of our ongoing research efforts in search for new anti-bacterial, hemolytic and antienzymatic agents [9,10], we report the pharmacological activities of

Results

Discussion

Conclusion