Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Biological screening and docking studies of unique hybrids synthesized by conventional versus microwave-assisted techniques

N A Virk¹, Aziz-ur-Rehman ¹ , M A Abbasi¹, S Z Siddiqui¹, A Ashraf², J Iqbal³, S Rasool¹, H Khalid⁴, S J Laulloo⁵, S U Khan⁶, S AA Shah^7,8

¹Department of Chemistry, Government College University, Lahore-54000; ²Department of Zoology, Government College University Faisalabad-38040; ³Department of Chemistry, University of Lahore-54600; ⁴Department of Chemistry, Forman Christian College University, Lahore-54600, Pakistan; ⁵Department of Chemistry, University of Mauritius, Reduit, Mauritius; ⁶School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor; ⁷Faculty of Pharmacy; ⁸Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.

For correspondence:- Aziz-ur-Rehman Email: azizryk@yahoo.com

Accepted: 14 April 2019 Published: 31 May 2019

Citation: Virk NA, A, Abbasi MA, Siddiqui SZ, Ashraf A, Iqbal J, et al. Biological screening and docking studies of unique hybrids synthesized by conventional versus microwave-assisted techniques. Trop J Pharm Res 2019; 18(5):1109-1117 doi: 10.4314/tjpr.v18i5.28

© 2019 The authors.
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Abstract

Purpose: To carry out the synthesis of various hybrids of 1,2,4-triazole in search of potential therapeutic enzyme inhibitory agents, and carry out docking and bovine serum albumin (BSA) binding studies on docking and bovine serum albumin (BSA) binding studies on the hybrids.

Methods: The target compounds were synthesized by following a multistep protocol. Compound 1 was synthesized from 4-methoxybenzenesulfonyl chloride (a) and ethyl isonipecotate (b). Compound 1 was refluxed with hydrazine to synthesize compound 2, which was converted to compound 3 through two consecutive steps. Compound 4 and different amines (5a-5i), were utilized to synthesize an array of electrophiles (6a-6i). A series of 1,2,4-triazole hybrids (7a-7i) were synthesized at room temperature by stirring together 3 and 6a-6i. The final structures of 7a-7i were elucidated through ¹H-NMR, ¹³C-NMR and EI-MS spectroscopy. The BSA binding studies were performed by fluorometric titration. Furthermore, antioxidant and enzyme inhibition activities were determined colorimetrically.

Results: Compound 7d was the most active antioxidant agent, compared to butylated hydroxyanisole (BHA), while compounds 7d, 7e, 7f, 7g and 7i proved to be potent urease inhibitors with half-maximal inhibitory concentration (IC₅₀) values of 19.5 ± 0.12, 21.1 ± 0.68, 18.2 ± 0.78, 19.9 ± 0.77 and 17.9 ± 0.10 µM, respectively, compared to thiourea with an IC₅₀ of 24.3 ± 0.24 µM. Compounds 7a, 7b, 7d, and 7e exhibited high butyrylcholinesterase inhibition potential, compared to eserine.

Conclusion: The synthesized compounds require studies further as potential therapeutic enzyme inhibitory agents in view of their urease inhibition as well as antioxidant activity.

Keywords: Ethyl isonipecotate, 1,2,4-Triazole, Urease inhibition, Butyrylcholinesterase inhibition