Delving into the Latest Updates on Radezolid with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Radezolid (USAN/INN), Radezolid Hydrochloride

+ [8]

Target

23S rRNA x 50S subunit

Action

modulators, inhibitors

Mechanism

23S rRNA modulators(23S Ribosomal RNA modulators), 50S subunit inhibitors(50S ribosomal subunit inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Mycobacterium Abscessus InfectionMRSA - Methicillin resistant Staphylococcus aureus infectionVancomycin-resistant enterococcal infection

Inactive Indication

AbscessCommunity Acquired PneumoniaComplicated skin and skin structure infection+ [2]

Originator Organization

Melinta Therapeutics, Inc.

Active Organization

Gyeongsang National UniversityMelinta Subsidiary Corp.

Inactive Organization

Melinta Therapeutics, Inc.

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC22H23FN6O3

InChIKeyBTTNOGHPGJANSW-IBGZPJMESA-N

CAS Registry869884-78-6

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.

16 Nov 2024·Critical Reviews in Analytical Chemistry

Analytical Methodologies for the Estimation of Oxazolidinone Antibiotics as Key Members of anti-MRSA Arsenal: A Decade in Review

Review

Author: Khafagy, El-Sayed ; El-Kimary, Eman I. ; Hegazy, Wael A. H. ; Allam, Ahmed N.

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.

31 Dec 2023·Journal of Enzyme Inhibition and Medicinal Chemistry

Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: in vitro , molecular docking, molecular dynamics, and SAR studies

Article

Author: Al‐Karmalawy, Ahmed A. ; Farouk, Faten ; Abourehab, Mohammed A. S. ; Elmaaty, Ayman Abo ; Saleh, Mohamed A. ; Elkamhawy, Ahmed ; Alnajjar, Radwan ; Tawfik, Haytham O. ; Eldehna, Wagdy M.

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.

100 Deals associated with Radezolid

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D09369	Radezolid	-	DB12339

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Mycobacterium Abscessus Infection	Preclinical	South Korea	Gyeongsang National University	26 Apr 2018
MRSA - Methicillin resistant Staphylococcus aureus infection	Preclinical	United States	Melinta Subsidiary Corp.	05 Jul 2008
Vancomycin-resistant enterococcal infection	Preclinical	United States	Melinta Subsidiary Corp.	05 Jul 2008
Abscess	Discovery	United States	Melinta Therapeutics, Inc.	01 Dec 2007
Complicated skin and skin structure infection	Discovery	United States	Melinta Therapeutics, Inc.	01 Dec 2007
Staphylococcal Skin Infections	Discovery	United States	Melinta Therapeutics, Inc.	01 Dec 2007
Streptococcal Infections	Discovery	United States	Melinta Therapeutics, Inc.	01 Dec 2007
Community Acquired Pneumonia	Discovery	Russia	Melinta Therapeutics, Inc.	01 Oct 2007
Community Acquired Pneumonia	Discovery	Canada	Melinta Therapeutics, Inc.	01 Oct 2007
Community Acquired Pneumonia	Discovery	United States	Melinta Therapeutics, Inc.	01 Oct 2007

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00640926 (CTgov)	Phase 2	Community Acquired Pneumonia	158	Radezolid (Radezolid 300 mg PO Daily (QD))	izsguxgczj(sqkcgokjxa) = doacalgsfc ideasydmiq (zdwhtzuwzk, ndwrzkvdrv - ufmurcgxpk) View more	-	04 Feb 2010
				Radezolid (Radezolid 450 mg PO Daily (QD))	izsguxgczj(sqkcgokjxa) = jtlhxyhwps ideasydmiq (zdwhtzuwzk, iufresdfaw - jdxnbsoozv) View more
NCT00646958 (CTgov)	Phase 2	Complicated skin and skin structure infection \| Abscess \| Streptococcal Infections \| Staphylococcal Skin Infections	150	Radezolid (Radezolid QD)	ihiqqsupei(rcchybkaxi) = jflmfxsisr dkxnaaspdb (uhfvcalriy, uiyvrxjcmo - sphiezihan) View more	-	26 Jun 2009
				Radezolid (Radezolid BID)	ihiqqsupei(rcchybkaxi) = toxiivvmez dkxnaaspdb (uhfvcalriy, czckykyqpf - oelrqyshjj) View more