Anti-Acne Activity of Minocycline Hybrids

Background: The Propionibacterium acnes (P. acnes) has been the most abundant acne causing bacteria on human skin. Tetracyclines and macrolides have been used against this bacterium. A need to develop newer antibiotics has been aroused due to point mutations in the genes of P. acnes. This work emphases our efforts to discover novel minocycline hybrids that fight against P. acnes. Nine hybrid compounds were synthesized using minocycline and naturally occurring aldehydes and ketones available from plant sources. Materials and Methods: In this study the antibacterial activity of the proposed minocycline hybrids was ascertained using web-application “antiBac-Pred” and in vitro antibacterial activity was processed using standards protocols against P. acnes. The zone of inhibition and minimum inhibitory concentration of synthesized compounds was determined by agar cup diffusion method and broth micro dilution method respectively and compared with standard drugs minocycline, chloramphenicol, ciprofloxacin and ampicillin. Results: The “antiBac-Pred” web application allowed us to predict that the designed minocycline hybrid can inhibit the growth of P. acnes based on the score of each compound expressed as confidence in its activity. The in vitro antibacterial activity showed promising results, with compound 2 demonstrating almost 4 times lower Minimum Inhibitory Concentration (MIC) for P. acnes and approximately 2 times lesser than minocycline, chloramphenicol, ciprofloxacin and ampicillin against P. acnes. Conclusion: Novel minocycline hybrids may serve as promising scaffolds which can be further optimized in terms of their Absorption Distribution Metabolism Excretion and Toxicity (ADMET) and be clinically utilized as an alternative for the treatment of bacterial infections due to P. acnes.