Radezolid

Gram-positive bacterial infections are among the most serious diseases related with high mortality rates and huge healthcare costs especially with the rise of antibiotic-resistant strains that limits treatment options. Thus, development of new antibiotics combating these multi-drug resistant bacteria is crucial. Oxazolidinone antibiotics are the only totally synthetic group of antibiotics that showed activity against multi-drug resistant Gram positive bacteria including MRSA because of their unique mechanism of action in targeting protein synthesis. This group include approved marketed members (tedizolid, linezolid and contezolid) or those under development (delpazlolid, radezolid and sutezolid). Due to the significant impact of this class, larger number of analytical methods were required to meet the needs of both clinical and industrial studies. Analyzing these drugs either alone or with other antimicrobial agents commonly used in ICU, in the presence of pharmaceutical or endogenous biological interferences, or in the presence of matrix impurities as metabolites and degradation products poses a big analytical challenge. This review highlights current analytical approaches published in the last decade (2012-2022) that dealt with the determination of these drugs in different matrices and discusses their advantages and disadvantages. Various techniques have been described for their determination including chromatographic, spectroscopic, capillary electrophoretic and electroanalytical methods. The review comprises six sections (one for each drug) with their related tables that depict critical figures of merit and some experimental conditions for the reviewed methods. Furthermore, future perspectives about the analytical methodologies that can be developed in the near future for determination of these drugs are suggested.

Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, molecular docking studies were used to investigate the binding interactions of 138 antibiotics against the human topoisomerase II-DNA complex. Followed by the MD simulations for 200 ns and MM-GBSA calculations. On the other hand, the antitumor activities of the most promising candidates were investigated against three cancer cell lines using doxorubicin (DOX) as a reference drug. Notably, spiramycin (SP) and clarithromycin (CL) showed promising anticancer potentials on the MCF-7 cell line. Moreover, azithromycin (AZ) and CL exhibited good anticancer potentials against the HCT-116 cell line. Finally, the TOP-2 enzyme inhibition assay was carried out to confirm the proposed rationale. Briefly, potent TOP-2 inhibitory potentials were recorded for erythromycin (ER) and roxithromycin (RO). Additionally, a SAR study opened eyes to promising anticancer pharmacophores encountered by these antibiotics.HighlightsMolecular docking studies of 139 antibiotics against the topoisomerase II-DNA complex.SP, RO, AZ, CL, and ER were the most promising and commercially available candidates.Molecular dynamics simulations for 200 ns for the most promising five complexes.MM-GBSA calculations for the frontier five complexes.SP and CL showed promising anticancer potentials on the MCF-7 cell line, besides, AZ and CL exhibited good anticancer potentials against the HCT-116 cell line.Potent TOP-2 inhibitory potentials were recorded for ER and RO.