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

• Published in: Tropical Journal of Pharmaceutical Research
• Main Author: Virk N.A.; Aziz-Ur-Rehman; Abbasi M.A.; Siddiqui S.Z.; Ashraf A.; Iqbal J.; Rasool S.; Khalid H.; Laulloo S.J.; Khan S.U.; Shah S.A.A.
• Format: Article
• Language: English
• Published: University of Benin 2019
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068772362&doi=10.4314%2ftjpr.v18i5.28&partnerID=40&md5=93f844ccbbaab7d5ea5beb00b0f60cbe

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 through1 H-NMR,13 C-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. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.