Ali, S., H.I. Faraag, A., Elgiushy, H., El-Mahdy, T., Askar, A., Hassan, A., Abouzid, K., Hammad, S. (2021). Synthesis, In Silico and In Vitro Antimicrobial Evaluation of Cyanoketene S,N-Acetals and their Pyrazoles Against Staphylococcus aureus DNA Gyrase Enzyme. Journal of Advanced Pharmacy Research, 5(3), 341-361. doi: 10.21608/aprh.2021.76173.1130
Shima Mahmoud Ali; Ahmed H.I. Faraag; Hossam R. Elgiushy; Taghrid S. El-Mahdy; Ahmed A. Askar; Ashraf S. Hassan; Khaled A. M. Abouzid; Sherif F. Hammad. "Synthesis, In Silico and In Vitro Antimicrobial Evaluation of Cyanoketene S,N-Acetals and their Pyrazoles Against Staphylococcus aureus DNA Gyrase Enzyme". Journal of Advanced Pharmacy Research, 5, 3, 2021, 341-361. doi: 10.21608/aprh.2021.76173.1130
Ali, S., H.I. Faraag, A., Elgiushy, H., El-Mahdy, T., Askar, A., Hassan, A., Abouzid, K., Hammad, S. (2021). 'Synthesis, In Silico and In Vitro Antimicrobial Evaluation of Cyanoketene S,N-Acetals and their Pyrazoles Against Staphylococcus aureus DNA Gyrase Enzyme', Journal of Advanced Pharmacy Research, 5(3), pp. 341-361. doi: 10.21608/aprh.2021.76173.1130
Ali, S., H.I. Faraag, A., Elgiushy, H., El-Mahdy, T., Askar, A., Hassan, A., Abouzid, K., Hammad, S. Synthesis, In Silico and In Vitro Antimicrobial Evaluation of Cyanoketene S,N-Acetals and their Pyrazoles Against Staphylococcus aureus DNA Gyrase Enzyme. Journal of Advanced Pharmacy Research, 2021; 5(3): 341-361. doi: 10.21608/aprh.2021.76173.1130
Synthesis, In Silico and In Vitro Antimicrobial Evaluation of Cyanoketene S,N-Acetals and their Pyrazoles Against Staphylococcus aureus DNA Gyrase Enzyme
1Department of Microbiology and Immunology, Faculty of Pharmacy, Helwan University, Egypt.
2Botany and Microbiology Department, Faculty of Science, Helwan University, Ain Helwan, Egypt.
3Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
4Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
5Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, Cairo, Egypt.
6Department of Organometallic and Organometalloid Chemistry, National Research Centre, Dokki 12622, Cairo, Egypt.
7Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
8Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 21934 Alexandria, Egypt.
Abstract
Objectives: The continuous reporting of bacterial resistance to antibiotics is an ongoing challenge that can be life-threatening. Actions to develop new chemicals to overcome the bacterial resistance has gained a significant importance. Methods: A series of ketene S,N-acetals 4a-k and their pyrazoles 6a-k were synthesized and their structures were established by spectral data. Membrane permeability predictions and in vitro antimicrobial activity against multi-drug resistant (MDR) Gram-positive bacteria and other microorganisms was determined. The binding affinity with DNA gyrase was assessed using in silico studies in comparison to ciprofloxacin then tthe gyrase inhibition assay was conducted to detect the mode of action. Results: All the synthesized compounds have a good affinity to pass through the phospholipid membrane of Staphylococcus aureus (S. aureus). Compound 6g exhibited the most potent antibacterial activity with MIC values ranged between 16 and 32 µg/mL. The compound also showed a higher binding affinity than ciprofloxacin with DNA gyrase in the in silico studies and this effect was clearly shown by a very good IC50 value of the gyrase inhibition assay. Conclusions: According to our data, compound 6g is a possible candidate to act against MDR bacteria and its main mode of action is through inhibition of the gyrase enzyme, further modifications are still required to enhance its activity.
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