Novel 2,3-disubstituted quinazoline-4(3H)-one molecules derived from amino acid linked sulphonamide as a potent malarial antifolates for DHFR inhibition

被引：47

作者：

Patel, Tarosh S. ^{[1
]}

Vanparia, Satish F. ^{[1
]}

Patel, Urmila H. ^{[2
]}

Dixit, Ritu B. ^{[3
]}

Chudasama, Chaitanya J. ^{[4
]}

Patel, Bhavesh D. ^{[5
]}

Dixit, Bharat C. ^{[1
]}

机构：

[1] Sardar Patel Univ, VP & RPTP Sci Coll, Dept Chem, Vallabh Vidyanagar 388120, Gujarat, India

[2] Sardar Patel Univ, Dept Phys, Vallabh Vidyanagar 388120, Gujarat, India

[3] Ashok & Rita Patel Inst Integrated Studies & Res, New Vallabh Vidyanagar 388121, Gujarat, India

[4] Sardar Patel Univ, Shree Alpesh N Patel PG Inst, Dept Biochem, Anand 388001, Gujarat, India

[5] Sardar Patel Univ, VP & RPTP Sci Coll, Dept Microbiol, Vallabh Vidyanagar 388120, Gujarat, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 129卷

关键词：

Triethylammonium acetate; p-LDH assay; MTT assay; Maestro; Glide; Cytotoxicity; DRUG-RESISTANCE; MICROWAVE-OVENS; DERIVATIVES; ANTICANCER; MECHANISM;

D O I：

10.1016/j.ejmech.2017.02.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：251 / 265

页数：15

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