Menaquinone is an essential component of the electron transport chain in many pathogens and consequently enzymes in the menaquinone biosynthesis pathway are potential drug targets for the development of novel antibacterial agents. Few years ago, Li et al.1 identified several 1,4-benzoxazine-2-one derivatives, that target MenB (1,4-dihydroxy-2-naphtoyl-CoA synthase), endowed with high antibacterial activity against Mycobacteria tuberculosis H37Rv with MIC values as low as 0.6 μg/ml. By these assumptions we designed and synthesized the corresponding isosters 1,4-benzoxazin-3-one derivatives in order to investigate the SAR of these novel compounds in comparision with the lead and with the purpose to improve the antimycobacterial activity also towards MOTT (Mycobacteria Other Than Tuberculosis) strains. Menaquinone is an essential component of the electron transport chain in many pathogens and consequently enzymes in the menaquinone biosynthesis pathway are potential drug targets for the development of novel antibacterial agents. Few years ago, Li et al.1 identified several 1,4-benzoxazine-2-one derivatives, that target MenB (1,4-dihydroxy-2-naphtoyl-CoA synthase), endowed with high antibacterial activity against Mycobacteria tuberculosis H37Rv with MIC values as low as 0.6 μg/ml. By these assumptions we designed and synthesized the corresponding isosters 1,4-benzoxazin-3-one derivatives in order to investigate the SAR of these novel compounds in comparision with the lead and with the purpose to improve the antimycobacterial activity also towards MOTT (Mycobacteria Other Than Tuberculosis) strains. Figure 1. Optimization of lead compound To date, the antimycobacterial activity is under investigation.

Novel 1,4-Benzoxazin-3-One Derivatives as Potential Antitubercular Compounds Targeting MenB Enzyme

ZAMPIERI, DANIELE;MAMOLO, MARIA GRAZIA;
2016

Abstract

Menaquinone is an essential component of the electron transport chain in many pathogens and consequently enzymes in the menaquinone biosynthesis pathway are potential drug targets for the development of novel antibacterial agents. Few years ago, Li et al.1 identified several 1,4-benzoxazine-2-one derivatives, that target MenB (1,4-dihydroxy-2-naphtoyl-CoA synthase), endowed with high antibacterial activity against Mycobacteria tuberculosis H37Rv with MIC values as low as 0.6 μg/ml. By these assumptions we designed and synthesized the corresponding isosters 1,4-benzoxazin-3-one derivatives in order to investigate the SAR of these novel compounds in comparision with the lead and with the purpose to improve the antimycobacterial activity also towards MOTT (Mycobacteria Other Than Tuberculosis) strains. Menaquinone is an essential component of the electron transport chain in many pathogens and consequently enzymes in the menaquinone biosynthesis pathway are potential drug targets for the development of novel antibacterial agents. Few years ago, Li et al.1 identified several 1,4-benzoxazine-2-one derivatives, that target MenB (1,4-dihydroxy-2-naphtoyl-CoA synthase), endowed with high antibacterial activity against Mycobacteria tuberculosis H37Rv with MIC values as low as 0.6 μg/ml. By these assumptions we designed and synthesized the corresponding isosters 1,4-benzoxazin-3-one derivatives in order to investigate the SAR of these novel compounds in comparision with the lead and with the purpose to improve the antimycobacterial activity also towards MOTT (Mycobacteria Other Than Tuberculosis) strains. Figure 1. Optimization of lead compound To date, the antimycobacterial activity is under investigation.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2886857
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