Synthesis, molecular docking and ADME prediction of some new benzimidazole carboxamidines derivatives as antimicrobial a
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Medicinal Chemistry Research https://doi.org/10.1007/s00044-020-02621-5
ORIGINAL RESEARCH
Synthesis, molecular docking and ADME prediction of some new benzimidazole carboxamidines derivatives as antimicrobial agents Meryem Erol
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Ismail Celik1,2 Ozlem Temiz-Arpaci2 Hakan Goker2 Fatma Kaynak-Onurdag3 Suzan Okten3 ●
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Received: 9 May 2020 / Accepted: 26 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In this study, 15 new 1H-benzimidazole-5-carboxamidine derivative compounds that could be new antimicrobial agents were synthesized and their antimicrobial activities were determined using the microdilution method. When the activity results were examined, it was observed that the antibacterial effects of the new benzimidazole derivatives were weaker than standard drugs, but some derivatives showed significant efficacy against MRSA and VREF with the value of MIC: 8 µg/ml compared to reference drugs. The antifungal effects of the compounds were found to be weaker compared to the reference drugs. Molecular docking studies of compounds and reference drugs used were performed against PBP4 and the active and allosteric site of PBP2a, and estimated ADME profiles were calculated. In addition, 2D and 3D interactions of N10, one of the most effective antimicrobial compounds compared to reference drugs, were demonstrated in both sites. Keywords Benzimidazole Carboxamidine Antimicrobial activity ADME prediction Molecular docking ●
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Introduction Infectious diseases seriously threaten public health, but the biggest problem in combating infectious diseases is the rapid development of resistance to existing drugs (Blair et al. 2015). Antimicrobial resistance is currently responsible for more than 700,000 deaths annually worldwide, and by 2050 it is estimated that it will reach an estimated economic cost of $100 million and more than 10 million deaths per year (Jansen et al. 2018). Resistance to antimicrobials (antibiotics, antifungals, antivirals, anthelmintics, antimalarials) leads to higher medical costs, treatment failure, increased mortality and morbidity, longer hospital stay, and
Supplementary information The online version of this article (https:// doi.org/10.1007/s00044-020-02621-5) contains supplementary material, which is available to authorized users. * Meryem Erol [email protected] 1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, 38280 Talas/Kayseri, Turkey
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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Yenimahalle/Ankara, Turkey
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Department of Pharmaceutical Microbiology, Faculty of Pharmacy, 22130 İskender/Edirne, Turkey
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increased disability. Without effective antimicrobials for the prevention and treatment of infections, many medical procedures such as organ transplantation, cancer treatment, diabetes and surgical operations become a high risk (Spellberg et al. 2013; Ventola 2015; Peters et al. 2019). In recent years, there has been an ala
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