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

• DOI: 10.1007/s00044-013-0707-0
• Publication Date: 2013-08-20T12:48:37Z
• Authors: Taibi Ben Hadda; Sajal Srivastava; Barnali Das; Héctor Salgado-Za...; Usama Shaheen; Ammar Bader; Muhammad Moazzam ...
• Keywords: Lipophilicity

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. 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.