Biology‐Oriented Drug Synthesis (BIODS) Approach towards Synthesis of Ciprofloxacin‐Dithiocarbamate Hybrids and Their Antibacterial Potential both in Vitro and in Silico

Abstract

A novel series of ciprofloxacin-dithiocarbamate hybrids 7a - 7l were designed, synthesized, and evaluated against Gram-positive and Gram-negative bacteria. A significant part of the title compounds showed considerable antibacterial activity against Gram-positive species. The most potent compound against Gram-positive bacteria was 2-chloro derivative 7h and the most potent derivative against Gram-negative bacteria was 3-chloro compound 7i. In vitro antibacterial evaluation of compound 7h against clinically isolated bacteria methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) showed that this compound acted better than ciprofloxacin against the latter bacteria. Docking study of compound 7h in the active site of S. aureus DNA gyrase revealed that this ciprofloxacin-dithiocarbamate derivative interacted with the main components of the active site of the enzyme.

Design and synthesis of new N-thioacylated ciprofloxacin derivatives as urease inhibitors with potential antibacterial activity

“…Ciprofloxacin-dithiocarbamate hybrid bearing ortho -chlorine group exhibited promising effects on the standard Gram-positive bacteria (Fig. 1 , compound A ) while changing the chlorine position from ortho to meta increased the activity against Gram-negative bacteria 28 . In silico assessment also demonstrated the important role of the sulfur atom through forming hydrogen bonds with the residues of S. aureus DNA gyrase 28 .…”

“…1 , compound A ) while changing the chlorine position from ortho to meta increased the activity against Gram-negative bacteria 28 . In silico assessment also demonstrated the important role of the sulfur atom through forming hydrogen bonds with the residues of S. aureus DNA gyrase 28 . Compound B is another example of a potent antimicrobial agent with ciprofloxacin moiety.…”

Novel fluoroquinolones containing 2‐arylamino‐2‐oxoethyl fragment: Design, synthesis, evaluation of antibacterial and antituberculosis activities and molecular modeling studies

“…In many researches, designed CFX hybrids have been synthesized, and their structure-activity relationships have been reported. [45][46][47][48] Besides that, CFX is used for the treatment of tuberculosis mainly in cases involving resistance or intolerance to first-line anti-TB therapy as the second-generation FQ drug. [36] Moxifloxacin (MFX), which is a fourth-generation FQ drug, has good bactericidal activity and is used for the treatment of a variety of infections.…”

Design, Synthesis and Antibacterial Studies of 1,3,4‐Oxadiazole‐Fluoroquinolone Hybrids and Their Molecular Docking Studies

“…Moreover, previous reports have demonstrated that incorporating bulky functional groups into this site exerts no apparent influence on the permeability of drugs to permeate through cell membrane, [9] providing a higher potential for antibacterial activity, lower incidence of being the target of efflux pumps, and decreased central nervous system (CNS) effects [10–12] . In this context, a large number of hybrids were built on fluoroquinolone skeleton, such as benzimidazole‐fluoroquinolone, [13] dithiocarbamate‐fluoroquinolone, [14,15] 1,2,4‐triazole‐ciprofloxacin hybrids with more superior activity than the parent drug against drug‐resistant bacteria, [16] fluoroquinolone‐flavonoid hybrids capable of inhibiting efflux pumps, [17] and piperazine‐azole‐fluoroquinolone hybrids maintaining the broad spectrum similar to that of ciprofloxacin [18] . Undoubtedly, modifications made at this position are promising for the discovery of novel fluoroquinolones antibiotics.…”