title: Novel 2,3-disubstituted quinazoline-4(3H)-one molecules derived from amino acid linked sulphonamide as a potent malarial antifolates for DHFR inhibition.
abstract: An optimization of a modified Grimmel's method for N-heterocyclization of Leucine linked sulphonamide leading to 2,3-disustituted-4-quinazolin-(3H)-ones was accomplished. Further, nineteen hybrid quinazolinone motifs (5a-5s) were synthesized by N-heterocyclization reaction under microwave irradiation using TEAA (IL) as green solvent as well as catalyst. The in vitro screening of the hybrid entities against the plasmodium species P. falciparum yielded five antimalarial potent molecules 5g, 5l, 5m, 5n &5p owing comparable activity to the reference drugs. The active scaffolds were further evaluated for enzyme inhibition efficacy against alleged receptor Pf-DHFR computationally as well as in vitro, proving their candidature as lead dihydrofolate reductase inhibitors. The prediction of the ADMET properties of the potent molecules also indicated their good oral bioavailability.
authors.affiliation: Chemistry Department, V. P. & R. P. T. P Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, India. Electronic address: tarosh_patel@yahoo.com.
authors.forename: Tarosh S
authors.initials: TS
authors.lastname: Patel
authors.affiliation: Chemistry Department, V. P. & R. P. T. P Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, India.
authors.forename: Satish F
authors.initials: SF
authors.lastname: Vanparia
authors.affiliation: Department of Physics, Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, India.
authors.forename: Urmila H
authors.initials: UH
authors.lastname: Patel
authors.affiliation: Ashok & Rita Patel Institute of Integrated Studies and Research in Biotechnology and Allied Sciences, New Vallabh Vidyanagar, 388121, Gujarat, India.
authors.forename: Ritu B
authors.initials: RB
authors.lastname: Dixit
authors.affiliation: Department of Biochemistry, Shree Alpesh N. Patel P. G. Institute, Affiliated to Sardar Patel University, Anand, 388001, Gujarat, India.
authors.forename: Chaitanya J
authors.initials: CJ
authors.lastname: Chudasama
authors.affiliation: Microbiology Department, V. P. & R. P. T. P Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, India.
authors.forename: Bhavesh D
authors.initials: BD
authors.lastname: Patel
authors.affiliation: Chemistry Department, V. P. & R. P. T. P Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar, 388 120, Gujarat, India. Electronic address: dixits20002003@yahoo.co.in.
authors.forename: Bharat C
authors.initials: BC
authors.lastname: Dixit
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D001682:Biological Availability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D013449:Sulfonamides / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase
chemical_list: D000596:Amino Acids; D000962:Antimalarials; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D011799:Quinazolines; D013449:Sulfonamides; D013762:Tetrahydrofolate Dehydrogenase
keywords: Cytotoxicity; Glide; MTT assay; Maestro; Triethylammonium acetate; p-LDH assay