Radezolid

New flurbiprofen linked 1,2,3-triazole and tetrazole scaffolds have been designed and synthesized using a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC).All the synthesized compounds were examined for the growth inhibition of HepG2, HuH7, MCF-7, and T-47D tumor cells and binding with focusing on the human cytochrome P 450 2C9 active site was investigated using mol. modeling.There was a strong correlation between the data from the docking studies and the biol. screening results.The cell lines that responded to the novel compound′s effects the best were HepG2 and MCF-7.Compound 5j was the most efficacious derivative among the four cancer cells (HepG2, HuH7, MCF-7, and T-47D) having IC₅₀ values of 1.89 ± 0.103, 2.86 ± 0.167, 1.66 ± 0.056, and 3.55 ± 0.045 μM, resp. and it had greater activity than doxorubicin.In addition, an in silico docking anal. was carried out to confirm the results of the experimentThe results highlight the potential of our triazole-bridged tetrazoles when combined with flurbiprofen (PDB: 1R9O) to enter the active site of human cytochrome P 450 2C9.The proposed binding mode of ligand 5 g was shown three hydrogen bonding via tetrazole with Glu427 (N24...OE1), triazole with Ala280 (N17...O) and fluoro group with Arg80 (F28...NH2) residues their internuclear distances are 2.89 Å, 2.71 Å, and 3.19 Å resp.Furthermore, the ADMET profile was assessed for each mol., and the findings of the in vitro and in silico investigations indicate that the triazoles incorporating tetrazole provide important new information for the creation of innovative anti-cancer treatments.

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.