title: Microwave Assisted Synthesis of Pyrimidines in Ionic Liquid and Their Potency as Non-Classical Malarial Antifolates.
abstract: Synthesis of pyrazole-linked triazolo-pyrimidine hybrids was achieved by employing Biginelli-type reaction methodology in an ionic liquid (triethylammonium acetate) under microwave irradiation. This method proved to be highly efficient and the ionic liquid employed was found recyclable for up to five consecutive cycles. The synthesized molecules were further screened for their antimalarial efficacy screening out the active scaffolds J15, J18, J21, J24, J27, and J30. The active molecules were evaluated in an enzyme inhibition study against the active Plasmodium falciparum dihydrofolate reductase (Pf-DHFR), computationally as well as in vitro, demonstrating their potency as DHFR inhibitors. The active entities were also investigated for their oral bioavailability by predicting ADME properties in silico, indicating good bioavailability.
authors.affiliation: Chemistry Department, V. P. & R. P. T. P. Science College, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India.
authors.forename: Jaimin D
authors.initials: JD
authors.lastname: Bhatt
authors.affiliation: Department of Biochemistry, Shree Alpesh N. Patel P. G. Institute, Sardar Patel University, Anand, Gujarat, India.
authors.forename: Chaitanya J
authors.initials: CJ
authors.lastname: Chudasama
authors.affiliation: Chemistry Department, V. P. & R. P. T. P. Science College, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India. drkdpatel64@yahoo.co.in.
authors.forename: Kanuprasad D
authors.initials: KD
authors.lastname: Patel
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D052578:Ionic Liquids / Q000737:chemistry*; D008872:Microwaves; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000201:enzymology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D052578:Ionic Liquids; D011743:Pyrimidines
keywords: ADMET; Docking; Glide; Pf-DHFR; Triethylammonium acetate