Structural classification of EZH2 inhibitors and prospects for the treatment of tumor: a review
AbstractZeste homolog enhancer 2 (EZH2) is one of the core catalytic subunits of PRC2, which mainly mediates histone H3K27 trimethylation to regulate the expression of tumor suppressor genes. Tazemetostat has been approved by the FDA as the first EZH2 inhibitor for the treatment of epithelioid sarcoma in 2020. In recent years, the role of EZH2 in tumor pathophysiology has been further studied, and more and more novel EZH2 inhibitors have been reported and applied in the treatment of lymphoma, prostate cancer, lung cancer and other cancers. In this article, we analyzed and summarized the structural features and the biologic...
Source: Medicinal Chemistry Research - June 19, 2023 Category: Chemistry Source Type: research
Pks 13 inhibitors —a promising target for future antitubercular agents
This article summarizes these classes of Pks 13 enzyme inhibitors exhibiting potential antitubercular activity along with their limitations and discusses the future scope.Graphical Abstract (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 17, 2023 Category: Chemistry Source Type: research
Synthesis and pharmacological evaluation of new disulfides linked to 1,2,4-triazole bearing urea moiety
AbstractThe present work involves the synthesis of a series of new disulfides linked to 1,2,4-triazole bearing urea moiety through multistep reaction. The in vitro cytotoxicity of the compounds in three human cancer cell lines (SMMC-7721, A549, Hela) and one normal cell line (L929) was evaluated via CCK-8 assay. Among the synthesized compounds, 3-(4-fluorophenylcarbamoylamino)-5-(n-butyldi-sulfanyl)-1,2,4-triazole (7c) was found to have the greatest antiproliferative activity against SMMC-7721 cells (IC50 = 1.10 µM) and showed better activity than the lead compound (PX-12, IC50 = 4.05 µM) and the reference dr...
Source: Medicinal Chemistry Research - June 16, 2023 Category: Chemistry Source Type: research
What ’s been Hapten-ing over the last 88 years?
AbstractDefinition of the relationship between drug protein adduct formation (haptenation) and development of immunological adverse drug reactions (drug hypersensitivity) has been an area of active research for over 80 years. The hapten hypothesis which states that “immunogenicity of low molecular weight organic chemicals is dependent on modification of self-proteins,” evolved from Landsteiner and Jacob’s discovery of a correlation between the reactivity of dinitro-halogenated benzenes and their sensitization potential. The hypothesis rapidly evolved to encompass drugs that often require metabolic activation to gener...
Source: Medicinal Chemistry Research - June 15, 2023 Category: Chemistry Source Type: research
Toxicology Modernization: Misnomer or Momentum
(Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 15, 2023 Category: Chemistry Source Type: research
Future challenges and opportunities with fluorine in drugs?
(Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 15, 2023 Category: Chemistry Source Type: research
Special issue of Medicinal Chemistry Research in honor of Dr. Nicholas A. Meanwell
(Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 15, 2023 Category: Chemistry Source Type: research
A MIST conception: what has been learned from twenty years of human metabolite safety assessment?
AbstractIn this review, we trace origins of the joint initiative of the pharmaceutical industry and major regulatory authorities to provide a framework for the identification, quantification, and testing of drug metabolites (i.e., Metabolites in Safety Testing; MIST). Dr. Tom Baillie was hugely instrumental in initiating and guiding this process and continues to be influential in this area up to present day. Current industry approaches to MIST are described, including evolution in techniques for metabolite identification, measurement, and characterization, plus a survey of contemporary technologies used to assess whether h...
Source: Medicinal Chemistry Research - June 13, 2023 Category: Chemistry Source Type: research
Design of novel amidoxime ketolide core and an efficient synthesis of WCK 4763: for treatment of gram-positive pneumococci
AbstractKetolides are the next generation macrolides, which shows broad spectrum of activity against macrolide resistant species,Streptococcus pneumoniae andStreptococcus pyogenes. Ketolides are derived from Erythromycin A, as name indicates; it possesses aC3 keto function after the replacement of cladinose sugar unit followed by oxidation. The early ketolide compounds are composed of 11,12 carbamate group andC11-12 aryl alkyl or 6-O alkyl extension. Here we report, further essentials in ketolide antibacterial drug development program carried out at Wockhardt, wherein pioneering synthetic strategies of novel amidoxime keto...
Source: Medicinal Chemistry Research - June 12, 2023 Category: Chemistry Source Type: research
A versatile strategy for the synthesis of various lumazine peptides
We report here a versatile and straightforward total synthesis of a series of lumazine peptides. Fluorescence titration experiments validate the metal binding characteristics of the synthesized compounds to Fe (III) and weak to no affinities to Cu (II), Co (II), and Mn (II).Graphical Abstract (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 10, 2023 Category: Chemistry Source Type: research
Semi-synthesis of novel thebaine derivatives with low cytotoxicity and their antibacterial and antihemolytic properties
AbstractIn the present study, some new 1,2,3-triazole-tethered analogs ofN-northebaine were designed and synthesized. The anti-bacterial properties of novel thebaine derivatives were studied onStaphylococcus aureus (S. aureus) andEscherichia coli (E. coli). Based on the results, compounds5b,5j and5m showed the best activities againstS. aureus (minimum inhibitory concentration (MIC) ~ 25 μM) compared to the parent compound (MIC ~ 321 μM). The most active anti-bacterial derivatives (i.e.,5b,5j and5m) and thebaine were considered as potent anti-bacterial wound healing agents. In this regard, fibroblast cell cyt...
Source: Medicinal Chemistry Research - June 10, 2023 Category: Chemistry Source Type: research
Novel indanone-chalcone esters with potential anti-Alzheimer effects designed using hybridization and bioisosteric replacement approaches
AbstractUsing molecular hybridization and bioisosteric replacement approaches, novel agents with potential use for the treatment of Alzheimer ’s disease (AD) were developed based on the structure of donepezil. A series of 14 indanone-chalcones bearing ester group were designed, synthesized, and then characterized using variety of methods. All target compounds showed moderate acetylcholinesterase (AChE) inhibitory potencies and among the m, the most active compound8e exhibited inhibitory activity with IC50 value of 18.7 µM against AChE. Also, Aβ1 –40 aggregation inhibitory activities of the synthesized compounds we...
Source: Medicinal Chemistry Research - June 9, 2023 Category: Chemistry Source Type: research
Design, synthesis, and antiproliferative activities of novel thiazolyl-pyrazole hybrid derivatives
In this study, a series of derivatives of thiazolyl-pyrazole hybrid structures were designed to search for new heterocyclic compound-based antitumor agents. The designed target structures were synthesized with easy, practical, and efficient procedures. The antiproliferative effect of the synthesized compounds against cancer cell lines A549, MCF-7, and HepG2 was evaluated regarding inhibition concentration and selectivity index against healthy cell line CCD-34Lu. The results overall showed that the compounds had high antiproliferation against cancer cells compared to the doxorubicin-positive control. In particular, compound...
Source: Medicinal Chemistry Research - June 8, 2023 Category: Chemistry Source Type: research
Discovery and exploration of monosaccharide linked dimers of galectin-3 inhibitors to target fibrosis
AbstractGalectin proteins have been targets of interest in numerous therapeutic areas for some time. Galectin-3 has been identified as a target of particular interest because of its unique structural characteristics and physiological profile. Recent literature indicates galectin-3 inhibition can decrease myofibroblast activation and procollagen expression with the potential to affect the progression of fibrosis in the lung, liver and kidney. Potential π-stacking interactions between one monosaccharide ligand bound to the carbohydrate recognition domain of a galectin-3 protein and a second ligand bound to a different galec...
Source: Medicinal Chemistry Research - June 8, 2023 Category: Chemistry Source Type: research
Successes in antiviral drug discovery: a tribute to Nick Meanwell
AbstractDrug discovery is a difficult task, and is even more challenging when the target evolves during therapy. Antiviral drug therapy is an excellent example, exemplified by the evolution of therapeutic approaches for treatment of hepatitis C and HIV-1. Nick Meanwell and his colleagues made important contributions leading to molecules for treatment of hepatitis C and HIV-1, each with distinct mechanisms of action. This review summarizes the discovery and impact of these drugs, and will highlight, where applicable, the broader contributions of these discoveries to medicinal chemistry and drug discovery. (Source: Medicinal Chemistry Research)
Source: Medicinal Chemistry Research - June 8, 2023 Category: Chemistry Source Type: research
