Synthesis and molecular docking of new N4-piperazinyl ciprofloxacin hybrids as antimicrobial DNA gyrase inhibitors

• Published in: Molecular diversity Vol. 27; no. 4; pp. 1751 - 1765
• Main Authors: Mohammed, Hamada H. H., Ali, Doaa Mohamed Elroby, Badr, Mohamed, Habib, Ahmed G. K., Mahmoud, Abobakr Mohamed, Farhan, Sarah M., Gany, Shimaa Salah Hassan Abd El, Mohamad, Soad A., Hayallah, Alaa M., Abbas, Samar H., Abuo-Rahma, Gamal El-Din A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-08-2023; Springer Nature B.V
• Subjects: Antibiotics; Antiparasitic agents; Biochemistry; Biomedical and Life Sciences; Cancer; Drug resistance; E coli; Ethanol; Life Sciences; Malaria; Organic Chemistry; Original; Original Article; Pharmacy; Polymer Sciences; Potash; Potassium; Antimicrobial; DNA gyrase inhibitors; Ciprofloxacin pyrimidine; Ciprofloxacin chalcone
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-022-10528-z

A series of
N
-4 piperazinyl ciprofloxacin derivatives as urea-tethered ciprofloxacin-chalcone hybrids
2a-j
and thioacetyl-linked ciprofloxacin-pyrimidine hybrids
5a-i
were synthesized. The target compounds were investigated for their antibacterial activity against
S. aureus
,
P. aeruginosa, E. coli,
and
C. albicans
strains, respectively. Ciprofloxacin derivatives
2a-j
and
5a-i
revealed broad antibacterial activity against either Gram positive or Gram negative strains, with MIC range of 0.06–42.23 µg/mL compared to ciprofloxacin with an MIC range of 0.15–3.25 µg/mL. Among the tested compounds, hybrids
2b
,
2c
,
5a, 5b
,
5h,
and
5i
exhibited remarkable antibacterial activity with MIC range of 0.06–1.53 µg/mL against the tested bacterial strains. On the other hand, compounds
2c
,
2e
,
5c,
and
5e
showed comparable antifungal activity to ketoconazole against
candida albicans
with MIC range of 2.03–3.89 µg/mL and 2.6 µg/mL, respectively. Further investigations showed that some ciprofloxacin hybrids have inhibitory activity against DNA gyrase as potential molecular target compared to ciprofloxacin with IC
50
range of 0.231 ± 0.01–7.592 ± 0.40 µM and 0.323 ± 0.02 µM, respectively. Docking studies of compounds
2b, 2c, 5b, 5c, 5e, 5h, and 5i
on the active site of DNA gyrase (PDB: 2XCT) confirmed their ability to form stable complex with the target enzyme like that of ciprofloxacin.
Graphical abstract