The Mutagenic Study of Benzimidazole Analogues: Structure-Activity Relationship (SAR)

Abstract

Event Abstract Back to Event The mutagenic study of benzimidazole analogues: structure-activity relationship (SAR) Nurul Hafizan Azahar1, Siti Soleha Abdullah1, Rozaini Abdullah2, Norizan Ahmat3 and Hasiah Ab Hamid1* 1 Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Malaysia 2 Department of Environmental and Occupational Health, Putra Malaysia University, Malaysia 3 School of Chemistry and Environment, University Technology Mara, Malaysia Background Benzimidazole analogues have diverse range of biological activities including anti-ulcer, anti-hypertensive, anti-viral, anti-fungal, anti-inflammatory and anti-cancer. Previous studies revealed some of the analogues can induce mutation despite their biological activities. This study aims to screen for potential mutagenic activities of novel benzimidazole analogues using Ames test and study their structure-activity relationship (SAR). Methods Ames test was carried out on two strains of Salmonella typhimurium; TA98 and TA100 that carry different mutations in their various genes in histidine operon, which protocols complied with OECD 471 Guideline for Testing of Chemicals. The preliminary tests including growth curve and genetic analysis were carried out prior to Ames test in order to determine the optimum incubation hour and genotypes of the bacterial strains respectively. The bacterial growth curve was carried out by incubating the bacterial suspension for 52 hours. The optical density of the bacteria was recorded for every two hours at 660nm wavelength and the graph of optical density versus time was plotted. The genotypes of the bacterial strains used were determined by genetic analysis which includes tests on dependency on histidine and/or biotin, presence of rfa mutation, urvB deletion as well as pKM101 plasmid. All data were analysed using Two-Way ANOVA, followed by post-hoc Tukey test. The SAR was analysed based on the results of Ames test. Results The optimum incubation hour for both strains was 14 hours. Both bacterial strains show dependency on histidine with presence of rfa mutation, urvB deletion and pKM101 plasmid. Besides, all analogues tested; NN-1-5, NN-1-7, NN-1-9 and NN-1-18 show no mutagenic activity. Conclusion There was no significant difference in the mutagenic activity among all analogues despite their difference in the number and position of hydroxyl groups. Keywords: benzimidazole, Ames test, Salmonella typhimurium, Structure-activity relationship (SAR), MUTAGENIC Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Cancer Citation: Azahar N, Abdullah S, Abdullah R, Ahmat N and Ab Hamid H (2019). The mutagenic study of benzimidazole analogues: structure-activity relationship (SAR). Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00012 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Hasiah Ab Hamid, Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Kuala Lumpur, Malaysia, hasiah@upm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nurul Hafizan Azahar Siti Soleha Abdullah Rozaini Abdullah Norizan Ahmat Hasiah Ab Hamid Google Nurul Hafizan Azahar Siti Soleha Abdullah Rozaini Abdullah Norizan Ahmat Hasiah Ab Hamid Google Scholar Nurul Hafizan Azahar Siti Soleha Abdullah Rozaini Abdullah Norizan Ahmat Hasiah Ab Hamid PubMed Nurul Hafizan Azahar Siti Soleha Abdullah Rozaini Abdullah Norizan Ahmat Hasiah Ab Hamid Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.