Chloropyrimidines as a new class of antimicrobial agents

被引:83
作者
Agarwal, N [1 ]
Srivastava, P [1 ]
Raghuwanshi, SK [1 ]
Upadhyay, DN [1 ]
Sinha, S [1 ]
Shukla, PK [1 ]
Ram, VJ [1 ]
机构
[1] Cent Drug Res Inst, Lucknow 226001, Uttar Pradesh, India
关键词
D O I
10.1016/S0968-0896(01)00374-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the course of our investigations of pyrimidines as antimycotic agents, we have identified a sub-class, with significant in vitro activity against mycobacteria. The salient feature of these pyrimidine derivatives (3a-o and 7a,b) is their appended aryl, heteroaryl and alkylthio substituent at position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of Mycobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 mug/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 mug/ mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 mug/mL. All the synthesized compounds were also evaluated for their antimycotic activity against five pathogenic fungi but only some of them 3j-n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:869 / 874
页数:6
相关论文
共 9 条
[1]   A NEW RAPID AND SIMPLE NONRADIOACTIVE ASSAY TO MONITOR AND DETERMINE THE PROLIFERATION OF LYMPHOCYTES - AN ALTERNATIVE TO [H-3] THYMIDINE INCORPORATION ASSAY [J].
AHMED, SA ;
GOGAL, RM ;
WALSH, JE .
JOURNAL OF IMMUNOLOGICAL METHODS, 1994, 170 (02) :211-224
[2]  
Bloom Barry R., 1994, TUBERCULOSIS PATHOGE
[3]   Microplate Alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium [J].
Collins, LA ;
Franzblau, SG .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (05) :1004-1009
[4]   DRUG-TREATMENT OF TUBERCULOSIS - 1992 [J].
DAVIDSON, PT ;
LE, HQ .
DRUGS, 1992, 43 (05) :651-673
[5]  
DHAR ML, 1968, INDIAN J EXP BIOL, V6, P232
[6]   CURRENT CONCEPTS - MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME [J].
HORSBURGH, CR .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (19) :1332-1338
[7]   5-CYANO-6-ARYLURACIL AND 2-THIOURACIL DERIVATIVES AS POTENTIAL CHEMOTHERAPEUTIC-AGENTS .4. [J].
RAM, VJ ;
VANDENBERGHE, DA ;
VLIETINCK, AJ .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1984, 21 (05) :1307-1312
[8]   CHEMOTHERAPEUTIC-AGENTS .12. SYNTHESIS OF PYRIMIDINES AND FUSED PYRIMIDINES AS LEISHMANICIDES AND HERBICIDES [J].
RAM, VJ .
JOURNAL FUR PRAKTISCHE CHEMIE, 1989, 331 (06) :893-905
[9]  
RAM VJ, 1987, LIEBIGS ANN CHEM, P797