Synthesis and antiparasitic activity of albendazole and mebendazole analogues (original) (raw)
Related papers
Synthesis and antiparasitic activity of 1 H-benzimidazole derivatives
Bioorganic & Medicinal Chemistry Letters, 2002
Compounds 1-18 have been synthesized and tested in vitro against the protozoa Giardia lamblia, Entamoeba histolytica and the helminth Trichinella spiralis. Inhibition of rat brain tubulin polymerization was also measured and compared for each compound. Results indicate that most of the compounds tested were more active as antiprotozoal agents than Metronidazole and Albendazole. None of the compounds was as active as Albendazole against T. spiralis. Although only compounds 3, 9 and 15 (2methoxycarbonylamino derivatives) inhibited tubulin polymerization, these were not the most potent antiparasitic compounds. #
Helminthiases, a group of neglected tropical diseases, affect more than one billion people mainly in tropical and subtropical regions. Albendazole (ABZ) is a broad‐spectrum anthelmintic recommended by the World Health Organisation (WHO). However, drug resistance is emerging due to its widespread use. In order to tackle this problem, taking into account the spectacular results obtained with the organometallic derivatization of the antimalarial drug chloroquine, we have prepared, in this study, a series of new ferrocenyl and ruthenocenyl derivatives of the organic drug ABZ and assessed their activity against different helminths but also protozoans, namely Trichuris muris adult, Heligmosomoides polygygrus adult, Schistosoma mansoni adult, Giardia lamblia, Haemonchus contortus xL3s and Toxoplasma gondii to determine the full potential of our new compounds. Worthy of note, the ferrocene‐containing ABZ analogue 2d exhibited over 70% activity against T. muris adult in vitro and no toxicity...
Molecules
Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H2N-BZM6, O2N-BZM7, and O2N-BZM9. The recombinant enzymes were used in inhib...
2000
Prc r arati nn or mctronidazo lc derivatives 2-5 is described and the results of antimicrobial evaluation and mutageni city arc givcn. Comrou nd s 2 and 5 at higher concentrati ons show better anti protozoal acti vity than thc parent drug. When tested again~t i'cw strain s of Burteroides f ragilis, an anaerobi c microorganism, compound 2 is found to be active o n four strains, l'lllllrOUIHI 4 to he active agai nst two strai n whereas 3 and 5 are effective against only one strain. In mutagenicity assay 4 is rou nd to hc I cs~ mut agcn ic th an the parent drug.
ChemInform, 2010
Prc r arati nn or mctronidazo lc derivatives 2-5 is described and the results of antimicrobial evaluation and mutageni city arc givcn. Comrou nd s 2 and 5 at higher concentrati ons show better anti protozoal acti vity than thc parent drug. When tested again~t i'cw strain s of Burteroides f ragilis, an anaerobi c microorganism, compound 2 is found to be active o n four strains, l'lllllrOUIHI 4 to he active agai nst two strai n whereas 3 and 5 are effective against only one strain. In mutagenicity assay 4 is rou nd to hc I cs~ mut agcn ic th an the parent drug.
Synthesis and Biological Evaluation of Metronidazole Derivatives as Anti-Giardia Agents
2015
Nitroimidazole derivatives such as Metronidazole (MTZ) have been used as anti- protozoa and anti-anaerobic bacteria. In this study several compounds of MTZ derivatives were synthesized and evaluated against Giardia lamblia cyst . Firs MTZ were reacted with several alkyl halide to obtain O-alkyl MTZ derivatives, then products were purified and their chemical structures were confirmed by elemental and spectral analysis ( 1 HNMR and Mass). In order to biological evaluation all compounds were investigated against 25 Giardia samples isolated from giarfdiasis patients. Results showed compound 2a had the most activity on cyst of Giardia in comparison with MTZ.
International Journal of Biological and Chemical Sciences, 2008
A novel series of 1,2,5-trisubstituted benzimidazole derivatives was synthesized by coupling 2-mercapto-5-methoxybenzimidazol-1-acetic acid with several amino acid methyl ester hydrochlorides/dipeptides/tripeptides using dicyclohexylcarbodiimide (DCC) as the coupling agent and triethylamine (TEA) as the base. All newly synthesized compounds were characterized by spectral as well as elemental analysis and evaluated for their biological potential. Compounds 5, 8 and 12 were found to exhibit potent anthelmintic activity against M. konkanensis, P. corethruses and Eudrilus sp. in comparison to standard drug-mebendazole. Moreover, compounds 7, 9 and 13 possessed potent antifungal activity against C. albicans and compounds 4 and 10 displayed good activity against pathogenic bacteria P. aeruginosa. Gram negative bacteria were found to be more sensitive in comparison to gram positive bacteria towards the newly synthesized benzimidazolopeptide analogs.
Synthesis and antiparasitic activity of 2-(Trifluoromethyl)benzimidazole derivatives
Bioorganic & Medicinal Chemistry Letters, 2001
AbstractÐ2-(Tri¯uoromethyl)benzimidazole derivatives substituted at the 1-, 5-, and 6-positions have been synthesized and in vitro tested against the protozoa Giardia lamblia, Entamoeba histolytica, and the helminth Trichinella spiralis. Results indicate that all the compounds tested are more active as antiprotozoal agents than Albendazole and Metronidazole. One compound (20) was as active as Albendazole against T. spiralis. These compounds were also tested for their eect on tubulin polymerization and none inhibited tubulin polymerization. #