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Chrysin based pyrimidine-piperazine hybrids: design, synthesis, in vitro antimicrobial and in silico E. coli topoisomerase II DNA gyrase efficacy

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Abstract

Ten chrysin-based pyrimidine-piperazine hybrids have been evaluated in vitro for antimicrobial activity against eleven bacterial and two fungal strains. All compounds 5a–j exhibited moderate to good inhibition, with MIC values ranging from 6.25 to 250 µg/ml. At 6.25 µg/ml and 12.5 µg/ml MIC values, respectively, compounds 5b and 5h demonstrated the most promising potency against E. coli, outperforming ampicillin, chloramphenicol, and ciprofloxacin. None of the substances had the same level of action as norfloxacin. 5a, 5d, 5g, 5h, and 5i have exhibited superior antifungal efficacy than Griseofulvin against C. albicans with 250 µg/ml MIC. All the compounds were also individually docked into the E. coli DNA gyrase ATP binding site (PDB ID: 1KZN) and CYP51 inhibitor (PDB ID: 5V5Z). The most active compound, 5h and 5g displayed a Glide docking score of − 5.97 kcal/mol and − 10.99 kcal/mol against DNA gyrase and 14α-demethylase enzyme CYP51 respectively. Potent compounds 5b, 5h, and 5g may be used to design new, innovative antimicrobial agents, according to in vitro, ADMET, and in silico biological efficacy analyses.

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Acknowledgements

The Sardar Vallabhbhai National Institute of Technology supported this research. The authors thank Mahrshee laboratory, Darshan health care, and Jaydev chemical for gifting piperazine derivatives. The authors are also thankful to the Micro care laboratory for the in vitro analysis of synthesized compounds. The authors are also grateful to Dr. Hitesh Patel and Gujarat University for the Schrodinger molecular modeling platform for molecular docking studies.

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Authors and Affiliations

  1. Department of Chemistry, Sardar Vallabhbhai National Institute of Technology, Surat, Gujarat, 395007, India

    Kajalben B. Patel & Premlata Kumari

  2. Microcare Laboratory, Surat, Gujarat, 395001, India

    Dhanji Rajani

  3. Department of Pharmaceutical Chemistry, Prof. Ravindra Nikam College of Pharmacy, Gondur, Dhule, Maharashtra, 424002, India

    Iqrar Ahmad

  4. Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India

    Iqrar Ahmad & Harun Patel

  5. Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, Gujarat, India

    Hitesh D. Patel

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Contributions

KBP: Conceptualization, Investigation, Writing—original draft, Drawing—Graphical abstract, and other figures. DR: Formal analysis. IA: Formal analysis. HP: Formal analysis HDP: Provide a platform for computational study. PK: Supervision, Writing—review and editing.

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Correspondence to Premlata Kumari.

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Patel, K.B., Rajani, D., Ahmad, I. et al. Chrysin based pyrimidine-piperazine hybrids: design, synthesis, in vitro antimicrobial and in silico E. coli topoisomerase II DNA gyrase efficacy. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10663-1

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