Novel menadione hybrids: Synthesis, anticancer activity, and cell‐based studies

Abstract

A series of novel menadione-based triazole hybrids were designed and synthesized by employing copper-catalyzed azide-alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data ( 1 H NMR, 13 C NMR, IR, and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU-145), cervical (Hela), breast (MCF-7), and mouse melanoma (B-16) using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity. Among the tested compounds, the triazoles 5 and 6 exhibited potent activity against all cell lines. In particular, compound 6 showed higher potency than the standard tamoxifen and parent menadione against MCF-7 cell line.Flow cytometric analysis revealed that compound 6 arrested cell cycle at G0/G1phase and induced apoptotic cell death which was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin-V-FITC assay. Thus, compound 6 can be considered as lead molecule for further development as potent anticancer therapeutic agent.

Anti-tubercular profile of new selenium-menadione conjugates against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain and multidrug-resistant clinical isolates

“…The considerable interest in these compounds is based on their pharmacological activities, especially as antimicrobial [ [8] , [9] , [10] , [11] ] and antitumor agents [ [12] , [13] , [14] , [15] ]. Most recently, 1,4-naphthoquinones, such as menadione (vitamin K3), have aroused a lot of interest due to relevant anticancer activity [ 16 ]. With specific attention on the anti-tubercular activity, studies have reported on the potential of using naphthoquinones as active agents against drug-resistant M. tuberculosis strains, although their mechanism of action has yet to be unveiled [ [17] , [18] , [19] ].…”

Comprehensive Analysis of Secondary Metabolites in Usnea longissima (Lichenized Ascomycetes, Parmeliaceae) Using UPLC-ESI-QTOF-MS/MS and Pro-Apoptotic Activity of Barbatic Acid

“…To validate whether barbatic acid ( 21 ) indeed caused apoptosis in A549 cells, we analyzed the nuclear fragmentation in treated cells, as one of the characteristics of apoptosis includes chromatin condensation and fragmentation of nuclei in inducing programmed cell death [32]. To achieve this, we treated A549 cells with 1 and 2 µM concentrations of barbatic acid for 48 h. Microscopic examination of Hoechst stained cells revealed chromatin condensation and fragmented nuclei indicating induction of apoptosis in A549 cells due to compound treatment (Figure 7).…”

“…After fixation cells were incubated with RNase A (0.1 mg/mL) at 37 °C for 30 min and stained with propidium iodide (Sigma Aldrich, St. Louis, MO, USA) (50 μg/mL) for 30 min on ice in dark. Cell cycle analysis was performed by flow cytometry (Becton Dickinson FACS Caliber instrument) [32].…”

Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking

“…Compared with clofazimine, it appears that menadione, which is also known as vitamin K3, has attracted more attention from the perspective of cancer treatment. Menadione has been identified to exhibit significant therapeutic benefits in the treatment of gastric cancer ( 55 ), prostate cancer ( 56 ), oral cancer ( 57 ) and breast cancer ( 58 ). Furthermore, the latest research indicated that menadione may increase anticancer activity by combining ROS-generating agents ( 59 ), but how it works in ESCA treatment requires further investigation.…”