Antimicrobial Activity of Some Novel Armed Thiophene Derivatives and Petra/Osiris/Molinspiration (POM) Analyses

Abstract

Tetrasubstituted 2-acetylthiophene derivative 5 was synthesized and then condensed with various nitrogen nucleophiles such as 5-amino-1,2,4-triazole, 2-aminobenzimidazole, aniline or p-chloroaniline to afford the corresponding iminothiophene derivatives 6-8a,b. Condensation of thiophene 5 with malononitrile as carbon nucleophile afforded compound 9, which underwent nucleophilic addition with DMF-DMA to afford compound 10. The newly synthesized products were characterized by elemental analysis, IR, MS, 1 H-13 C-NMR and CHN analysis and then evaluated for their antimicrobial activity. Results of the in vitro antibacterial activity showed that thiophene derivative 7 was found to be more potent than the standard drug gentamicin against Pseudomonas aeruginosa. Some of these compounds showed potential antimicrobial activities. Molecular docking and Osiris/Molinspiration analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution with electronic donor group doesn't guarantee more effective bioactivity. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.

Synthesis, characterization, X-ray structure, computational studies, and bioassay of novel compounds combining thiophene and benzimidazole or 1,2,4-triazole moieties

“…The disc diffusion method [21] was used in this assay and each experiment was performed in triplicate; experimental details of these techniques can be found elsewhere [22, 23]. Readings of the zone of inhibition, which are shown in Table 4, represent the mean value of three readings.…”

Molecular design, synthesis and biological characterization of novel Resveratrol derivative as potential anticancer agent targeting NF-κB

“…Hence, the determination of the molecular properties of these bioactive compounds is important for discovering and developing new drugs. In this study, molinspiration computational webserver (http://www.molinspiration.com/cgi-bin/properties; Mabkhot et al, 2016) was used to determine the drug-likeliness properties of RESV analogs. The chemical structure of the query compound either in manually designed or in SMILES formats are provided to this webserver to calculate its molecular characteristics like total polar surface area (TPSA), range of atoms (natoms), molecular size (mass), number of hydrogen bond acceptors (range of O or N), partition coefficient (miloP), range of rotatable bonds (nrotb), volume of drug distribution (molecular volume) and number of hydrogen bond donors (range of OH) (Lipinski, 2004).…”

Thiophene Scaffold as Prospective Antimicrobial Agent: A Review

“…Suitable substitution at position 5 of thiophene ring of the synthesized derivatives (Fig. ) improves the antibacterial activity .…”

“…Mabkhot et al . synthesized thiophene derivatives from 5‐acyl‐4‐phenyl‐2‐(phenyl‐amino)thiophene‐3‐carboxylate as precursor . These derivatives were subjected to antibacterial activity screening against Gram‐positive bacteria, namely, B. subtilis and S. pneumoniae , and Gram‐negative bacteria, namely, E. coli and P. aeruginosa .…”