In Vitro Antibacterial and Antifungal Activity and Computational Evaluation of Novel Indole Derivatives Containing 4-Substituted Piperazine Moieties

Abstract

Background: Lack of specificity and occurence of resistance to current antibacterial and antifungal agents are major shortcomings for the treatment of microbial diseases. Finding novel antimicrobial agents is therefore highly needed to develop more potent drugs. Within this framework, several indole derivatives were designed and reported in the literature. Methods: In vitro antibacterial and antifungal activities of previously synthesized novel indole compounds containing 4-substituted piperazine moieties were tested against Staphylococcus aureus (ATCC 25923), Methicilline resistant Staphylococcus aureus (MRSA, ATCC 43300), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633) and Candida albicans (ATTC 10231). Sultamicillin T, ampicillin, ciprofloxacin and fluconazole were used as positive controls. Molecular docking was used to study the interaction of active compounds with their receptor. Results: Fifteen compounds were synthesized and their antibacterial activities were similar to that of the reference drugs used as controls. Compounds 4 and 15 were more active (MIC 25 µg/ml) than ampicillin (MIC 50 µg/ml) against MRSA, while they showed the same activity as sultamicillin T (MIC 25 µg/ml). All compounds showed lower activity than ciprofloxacin (MIC 25 µg/ml) against the tested microorganisms. However, none of the compounds showed remarkable antifungal activity against C. albicans. Conclusion: Compound 6 showed the best interaction with the amino acid residues of the targeted cofactor NAD+. Keywords: Antibacterial, antifungal, piperazine, indole, docking, ciprofloxacin.