Chemical synthesis and molecular modeling of novel substituted N-1,3-benzoxazol-2yl benzene sulfonamides as inhibitors o
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ORIGINAL PAPER
Chemical synthesis and molecular modeling of novel substituted N‑1,3‑benzoxazol‑2yl benzene sulfonamides as inhibitors of inhA enzyme and Mycobacterium tuberculosis growth Narendra Singh Chundawat1 · Gajanan S. Shanbhag1 · Narendra Pal Singh Chauhan1 Received: 30 June 2020 / Accepted: 29 September 2020 © Iranian Chemical Society 2020
Abstract Tuberculosis (TB) is one of the major contagious diseases with high mortality which is caused by Mycobacterium tuberculosis (Mtb) pathogen. Due to the existing antibiotic resistance (MDR-TB) to tuberculosis, the demand for the development of new potential chemotherapy drugs is increasing. Herein, we report synthesis of two novel benzoxazole-based series, namely 2-phenyl benzoxazole sulfonamide and 2-piperidine-benzoxazole sulfonamides. These compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv strain, using the microplate alamarBlue assay. Molecular docking studies were carried out to comprehend the binding mode of the compounds. It is evident from molecular docking studies and minimum inhibitory concentration assay (MIC) that 2-phenyl benzoxazole sulfonamide scaffold has a greater potential of antitubercular activity possibly by ENR inhibition (inhA inhibitors). In silico cytotoxicity studies using CLC-Pred tool database suggested that both the series were relatively safe. Graphic abstract In silico CLC-Pred cell line cytotoxicity prediction
N O
O N S O
Mycobacterium tuberculosis (MTB)-MABA Assay
Diversity 2 Br
N
N
Diversity 1
O Br
Benzoxazole
Compound 8
Compound 20 HEK293 Cell line(Embryonic kidney ): Pa 0.862 /Pi 0.004
MIC:
N
NH O O S O
1.6µg/mL
O
Me
NH O S
O
Compound 11
Me
3.12µg/mL
Keywords Mycobacterium tuberculosis · Benzoxazole sulfonamide · Antitubercular activity · inhA inhibitors · Molecular docking · Cytotoxicity
Introduction Tuberculosis (TB) which is caused by Mycobacterium tuberculosis is one of the prime infectious diseases in human beings Bogatcheva et al. [1]. It is responsible for the second highest cause of death for humans following human * Gajanan S. Shanbhag [email protected] 1
Department of Chemistry, Bhupal Nobles’ University, Udaipur, Rajasthan, India
immunodeficiency virus/AIDS. Ever since 1993, TB has been recognized as a global health emergency by the World Health Organization. TB causes more than nine million new cases annually with a casualty of about 1.8 million people worldwide every year. In modern era, numerous drugs have emerged, for eradicating TB. However, resistance to those drugs is an alarming matter. Due to recurring incidences of multidrug-resistant (MDR-TB) and extensively drugresistant (XDR) strains of M. tuberculosis, there is a global necessity to develop new age chemotherapeutics to battle different forms of TB Rattan et al. [2].
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Journal of the Iranian Chemical Society
Mycolic acid is a basic component of mycobacterial cell wall present in the FAS (fatty acid synthase) system of human pathogen M. tube
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