Diarylpyrazole Ligated Dihydropyrimidine Hybrids as Potent Non-Classical Antifolates and Their Efficacy Against Plasmodium falciparum

作者：Bhatt Jaimin D; Chudasama Chaitanya J; Patel Kanuprasad D

来源：Archiv der Pharmazie, 2017, 350(9): e1700088.

DOI：10.1002/ardp.201700088

• Glide
• MTT assay
• Pf-DHFR
• Triethylammonium acetate
• Vero cells

A series of diarylpyrazole clubbed dihydropyrimidine derivatives (J1-J30) was synthesized under microwave-assisted heating conditions by employing Biginelli reaction methodology and utilizing triethylammonium acetate both as a catalyst and as reaction medium, leading towards a greener reaction pathway. The synthesized entities were screened for their antimalarial efficacy against a Plasmodium falciparum strain in vitro. The active entities (J9, J15, J21, J25, and J27) obtained out of the in vitro screening were further evaluated for their enzyme inhibitory potency against the Pf-DHFR enzyme in vitro as well as in silico using Glide. Furthermore, the active scaffolds were tested for their cytotoxicity against Vero cells, proving their nontoxic behavior and selectivity. The ADME parameters were also evaluated and predicted in silico, indicating good oral bioavailability of the compounds.

• 出版日期2017-9