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POM analyses of antimicrobial activity of some 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes: favourable and unfavourable physico-chemical parameters in design of antibacterial and mycolytic agents

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Abstract

In the present contribution, we have used petra, osiris and molinspiration (POM) analyses to identify pharmacophores and anti-pharmacophores for antibacterial/antifungal activity of some benzothiophene derivatives (THBT). Lipophilicity and presence of tautomerism processes were the major factors that governed the orientation to antibacterial and/or antiviral activity. It was also observed that these compounds POM analyzed have a closed pharmacophore site which might be bioactivity low. Further, we have carried out receptor-based electrostatic analysis to confirm the electronic, steric and hydrophobic requirements for future modifications. The POM analyses provide substantial idea about the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the drug-resistant microorganisms.

Graphical Abstract

The impact of intramolecular OH/N and NH/N interactions on bioactivity of pharmacophores sites of THBT series 5–15 is established. The POM analyses of 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes (THBT) 5–15 provide substantial idea about the structural features responsible for their failure as dual antibacterial/antifungal agents and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the bacterial and fungal enzymes responsible of diseases.

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Acknowledgments

Prof. T. Ben Hadda would like to thank ACTELION; the Biopharmaceutical Company of Swiss, for molecular properties calculations.

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Authors and Affiliations

  1. Laboratoire de Chimie des Matériaux, Faculté des Sciences, Université Mohammed Premier, 60000, Oujda, Morocco

    Taibi Ben Hadda

  2. Department of Medicinal Chemistry, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, India

    Sajal Srivastava

  3. School of Pharmaceutical Education & Research, Berhampur University, Berhampur, Odisha, India

    Barnali Das

  4. Departamento de Química Orgánica, ENCB, Instituto Politécnico Nacional, Prol. Carpio y Plan de Ayala s/n, Col. Santo Tomás, 11340, Mexico, DF, Mexico

    Héctor Salgado-Zamora

  5. Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia

    Usama Shaheen & Ammar Bader

  6. Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Muhammad Moazzam Naseer

Authors
  1. Taibi Ben Hadda
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  2. Sajal Srivastava
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  3. Barnali Das
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  4. Héctor Salgado-Zamora
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  5. Usama Shaheen
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  6. Ammar Bader
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  7. Muhammad Moazzam Naseer
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Correspondence to Taibi Ben Hadda.

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Hadda, T.B., Srivastava, S., Das, B. et al. POM analyses of antimicrobial activity of some 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes: favourable and unfavourable physico-chemical parameters in design of antibacterial and mycolytic agents. Med Chem Res 23, 995–1003 (2014). https://doi.org/10.1007/s00044-013-0707-0

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  • DOI: https://doi.org/10.1007/s00044-013-0707-0

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