Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence

Author:

Katiyar S K1,Gordon V R1,McLaughlin G L1,Edlind T D1

Affiliation:

1. Medical College of Pennsylvania, Philadelphia 19129.

Abstract

Benzimidazoles have been widely used since the 1960s as anthelmintic agents in veterinary and human medicine and as antifungal agents in agriculture. More recently, selected benzimidazole derivatives were shown to be active in vitro against two protozoan parasites, Trichomonas vaginalis and Giardia lamblia, and clinical studies with AIDS patients have suggested that microsporidia are susceptible as well. Here, we first present in vitro susceptibility data for T. vaginalis and G. lamblia using an expanded set of benzimidazole derivatives. Both parasites were highly susceptible to four derivatives, including mebendazole, flubendazole, and fenbendazole (50% inhibitory concentrations of 0.005 to 0.16 microgram/ml). These derivatives also had lethal activity that was time dependent: 90% of T. vaginalis cells failed to recover following a 20-h exposure to mebendazole at 0.17 microgram/ml. G. lamblia, but not T. vaginalis, was highly susceptible to five additional derivatives. Next, we examined in vitro activity of benzimidazoles against additional protozoan parasites: little or no activity was observed against Entamoeba histolytica, Leishmania major, and Acanthamoeba polyphaga. Since the microtubule protein beta-tubulin has been identified as the benzimidazole target in helminths and fungi, potential correlations between benzimidazole activity and beta-tubulin sequence were examined. This analysis included partial sequences (residues 108 to 259) from the organisms mentioned above, as well as the microsporidia Encephalitozoon hellem and Encephalitozoon cuniculi and the sporozoan Cryptosporidium parvum. beta-tubulin residues Glu-198 and, in particular, Phe-200 are strong predictors of benzimidazole susceptibility; both are present in Encephalitozoon spp. but absent in C. parvum.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference29 articles.

1. Mebendazole in giardial infections: a comparative study with metronidazole;Al-Waili N. S. D.;J. Infect. Dis.,1992

2. Treatment of intestinal microsporidiosis with albendazole in patients with AIDS;Blanshard C.;AIDS,1992

3. In-vitro susceptibility of Giardia lamblia to albendazole, mebendazole and other chemotherapeutic agents;Cedillo-Rivera R;J. Med. Microbiol.,1992

4. Giardia lamblia: ultrastructural study of the in vitro effect of benzimidazoles;Chavez B.;J. Protozool.,1992

5. Effects of albendazole on Entamoeba histolytica and Giardia lamblia;Chavez B.;Arch. Med. Res.,1992

Cited by 184 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Perspectives on the drug discovery of intestinal protozoan parasites;Intestinal Parasites - New Developments in Diagnosis, Treatment, Prevention and Future Directions [Working Title];2024-06-04

2. Effects of Mebendazole on the Caspase–mediated Apoptosis mechanism in Cancer cell culture;Revista Científica de la Facultad de Ciencias Veterinarias;2024-03-30

3. Benzimidazoles in helminthiasis chemotherapy: Developments and challenges;Journal of Molecular Structure;2024-01

4. Screening of the Pandemic Response Box identifies anti-microsporidia compounds;PLOS Neglected Tropical Diseases;2023-12-08

5. Phenolic chalcones as agents against Trichomonas vaginalis;Bioorganic Chemistry;2023-12

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3