Design,synthesis and molecular docking of new N-4-piperazinyl ciprofloxacin-triazole hybrids with potential antimicrobial activity
Affiliation:
1. Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Deraya University, New-Minia 61519, Egypt;3. Deprtment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA;4. Bacteriology Division, Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose 204-8533, Japan;5. Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan;6. Department of Microbiology & Immunology, Faculty of Pharmacy, Minia University, Minia 61519, Egypt;1. Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India;2. Department of Biotechnology, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India;3. Department of Botany, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India;1. Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia;2. Pesticide Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt;3. Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA;4. Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA;5. Microbiology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt;6. Peptide Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt;7. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia;8. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt;1. School of Chemistry and Materials Science, Hubei Engineering University, Hubei, PR China;2. Pony Testing International Group (Wuhan), Wuhan, 430000, PR China;3. Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, Wuhan University of Science and Technology, Hubei, PR China;4. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China;5. WuXi AppTec (Wuhan), Hubei, PR China;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt;2. Department of Microbiology, Faculty of Pharmacy, October 6 University, 6 October City 12585, Giza, Egypt;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, October 6 University, 6 October City 12585, Giza, Egypt;1. School of Nuclear Technology and Chemistry & Life Science, Hubei University of Science and Technology, Hubei, PR China;2. Pony Testing International Group (Wuhan), Hubei, PR China;3. Zhejiang Xianju Junye Pharmaceutical Co., Ltd, Xianju, Zhejiang, 317300, PR China;4. School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei, 430081, PR China;5. Synthetic and Functional Biomolecules Center, Peking University, Beijing, PR China
Abstract:
New N-4-piperazinyl ciprofloxacin-triazole hybrids 6a-o were prepared and characterized. The in vitro antimycobacterial activity revealed that compound 6a experienced promising antimycobacterial activity against Mycobactrium smegmatis compared with the reference isoniazide (INH). Additionally, compound 6a exhibited broad spectrum antibacterial activity against all the tested strains either Gram-positive or Gram-negative bacteria compared with the reference ciprofloxacin. Also, compounds 6g and 6i displayed considerable antifungal activity compared with the reference ketoconazole. DNA cleavage assay of the highly active compounds 6c and 6h showed a good correlation between the Mycobactrium cleaved DNA gyrase assay and their in vitro antimycobactrial activity. Moreover, molecular modeling studies were done for the designed ciprofloxacin derivatives to predict their binding modes towards Topoisomerase II enzyme (PDB: 5bs8).
