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Design and development of pyrrole carbaldehyde: an effective pharmacophore for enoyl-ACP reductase

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Abstract

Enoyl-ACP reductase is the key enzyme involved in FAS-II synthesis of mycolic acid in bacterial cell wall and is a promising target for discovering new chemical entity. The designed pharmacophores are the possible better tools to combat mutation in enoyl-ACP enzyme, which leads to a decrease in volume of triclosan binding site. Compound 3a showed H-bonding interactions similar to that of triclosan with enoyl-ACP enzyme and with a better docking score (C score 8.81), while the compound 3f showed additional interaction with MET98.H amino acid residue. The 3D-QSAR computations also support the docking study to develop novel pyrrole-based derivatives.

Graphical abstract

Molecular docking 3D-QSAR studies and synthesis of active analogs of pyrrole carbaldehyde as better receptor fit pharmacophore for enoyl-ACP reductase along with in vitro antitubercular activity.

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Acknowledgments

Authors immensely thank research support from the Board of Research in Nuclear Sciences (BRNS), Bhabha Atomic Research Centre (BARC), Mumbai (File No. 2013/37B/17/BRNS/0417 dated-14/05/2013). We also thank Dr. V. H. Kulkarni, Principal and Mr. H. V. Dambal, President, S.E.T’s College of Pharmacy, Dharwad, India for providing the facilities. The authors are grateful to Mr. Ravindra N. Nadagir and Mr. Shrikant A. Tiwari for their technical assistance.

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Authors and Affiliations

  1. Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S.E.T’s College of Pharmacy, Sangolli Rayanna Nagar, Dharwad, 580 002, India

    Shrinivas D. Joshi, Devendra Kumar, Uttam A. More & Tejraj M. Aminabhavi

  2. Department of Polymer and Fiber System Engineering, Chonnam National University, 300 Yongbong-Dong, Bukgu, Gwangju, 500 757, Korea

    Kap Seung Yang

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  1. Shrinivas D. Joshi
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  2. Devendra Kumar
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  3. Uttam A. More
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Correspondence to Shrinivas D. Joshi.

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Joshi, S.D., Kumar, D., More, U.A. et al. Design and development of pyrrole carbaldehyde: an effective pharmacophore for enoyl-ACP reductase. Med Chem Res 25, 672–689 (2016). https://doi.org/10.1007/s00044-016-1517-y

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