Design and development of novel N‐(4‐aminobenzoyl)‐ l‐glutamic acid conjugated 1, 3, 5‐triazine derivatives as Pf‐DHFR inhibitor: An in‐silico and in‐vitro study. Issue 4 (21st December 2022)

• Record Type: Journal Article
• Authors: Adhikari, Nayana; Choudhury, Ayesha A. K.; Shakya, Anshul; Ghosh, Surajit K.; Patgiri, Saurav J.; Singh, Udaya P.; Bhat, Hans R.
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 37:Issue 4(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-21
• Subjects: 1, 3, 5‐triazine -- antimalarial -- docking -- N‐(4‐aminobenzoyl)‐l‐glutamic acid -- Pf‐DHFR‐TS; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.23290
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: In the present work, a library of 120 compounds was prepared using various aliphatic and aromatic amines. Finally, 10 compounds were selected through in silico screening carrying 4‐aminobenzoyl‐l ‐glutamic acid and 1, 3, 5‐triazine moiety. The docking results of compounds 4d16 and 4d38 revealed higher binding interaction with amino acids Asp54 (−537.96 kcal/mol) and Asp54, Phe116 (−618.22 kcal/mol) against wild (1J3I) and quadruple mutant (1J3K) type of Pf ‐DHFR inhibitors and were comparable to standard WR99210. These compounds were developed by facile and microwave‐assisted synthesis via nucleophilic substitution reaction and characterized by different spectroscopic methods. In vitro antimalarial assay results also suggested that these two compounds were having higher antimalarial activity against chloroquine‐sensitive (3D7) and chloroquine‐resistant (Dd2) strain out of the ten synthesized compounds with IC50 13.25 μM and 14.72 μM, respectively. These hybrid scaffolds might be useful in the lead discovery of a new class of Pf ‐DHFR inhibitors.