Tyrosine kinase inhibitors (TKIs) have markedly improved the overall survival rate of patients with chronic myeloid leukemia (CML), enabling them to achieve a normal life expectancy. However, toxicity, relapse, and drug resistance continue to pose major challenges in the clinical treatment of CML. The progression of leukemia is directly connected to higher expression levels and enzymatic actions of matrix metalloproteinase-2 (MMP-2).
View Article and Find Full Text PDFACS Appl Bio Mater
December 2024
Lipid droplets (LD) are crucial in pathological processes or conditions associated with abnormal lipid metabolism, such as obesity, diabetes, atherosclerosis, fatty liver diseases, and cancers. Cancer cells frequently contain elevated levels of nonpolar lipid droplets (LDs), serving as energy reserves. The proliferation of LDs, accompanied by an increase in viscosity, is a characteristic feature of cancer cells that prompted us to devise a fluorescent sensor for LD detection at physiological pH.
View Article and Find Full Text PDFHerein, we report the synthesis and anticancer properties of 21 new 1,3,4-thiadiazole-2-yl-imino-thiazolidine-4-one containing binary heterocyclic molecules. Cytotoxicity of the synthesized molecules was evaluated on various cancer cell lines (MCF-7, PC3, 4T1, MDA-MB-231, and MOC2) and normal human embryonic cell lines (HEK-293) MTT assay. The cytotoxicity data of developed compounds was compared with the reference anticancer molecule BG45, a selective inhibitor of the HDAC3 enzyme.
View Article and Find Full Text PDFOverexpression of matrix metalloproteinase-2 (MMP-2) possesses a correlation with leukemia especially chronic myeloid leukemia (CML). However, no such MMP-2 inhibitor has come out in the market to date for treating leukemia. In this study, synthesis, biological evaluation, and molecular modeling studies of a set of biphenylsulfonamide derivatives as promising MMP-2 inhibitors were performed, focusing on their potential applications as antileukemic therapeutics.
View Article and Find Full Text PDFChronic myeloid leukemia (CML) is a global issue and the available drugs such as tyrosine kinase inhibitors (TKIs) comprise various toxic effects as well as resistance and cross-resistance. Therefore, novel molecules targeting specific enzymes may unravel a new direction in antileukemic drug discovery. In this context, targeting gelatinases (MMP-2 and MMP-9) can be an alternative option for the development of novel molecules effective against CML.
View Article and Find Full Text PDFHDAC3 modulation shows promise for breast cancer, including triple-negative cases. Novel -hydrazide-based HDAC3 inhibitors were designed and synthesized. Lead compound exhibited potent HDAC3 inhibition (IC = 14 nM) with at least 121-fold selectivity.
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