Ferrocene-based modulators of cancer-associated tumor pyruvate kinase M2

• Published in: Journal of organometallic chemistry Vol. 968-969; pp. 122338 - 122351
• Main Authors: Jadhav, Jyotika, Das, Rudradip, Kamble, Sayali, Chowdhury, Moumita Ghosh, Kapoor, Saumya, Gupta, Astha, Vyas, Het, Shard, Amit
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 01.06.2022; Elsevier
• Subjects: Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Cyclic voltammetry; Cytotoxicity; FE-SEM; Physical Sciences; Pyruvate kinase M2; Science & Technology; Single crystal X-RD; Triazolopyrimidine; FTP; Single crystal X-RD; LUMO; Cytotoxicity; TLC; EGFR; Cyclic voltammetry; HRMS; LDH; MESP; JAHA; DFT; DASA; EDS; IC50; CF-1; ESI; Pyruvate kinase M2; AC50; PKM2; FESEM; B3LYP; FMO; SCX-RD; CV; DNA; ROS; TBAPF; FE-SEM; Triazolopyrimidine; PEP; TMS; MCR; ANTICANCER ACTIVITY; COMPLEXES
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/j.jorganchem.2022.122338

•Novel and skeletally diverse ferrocene-based triazolopyrimidines were synthesized using a multicomponent reaction.•The compounds exhibited excellent tumor pyruvate kinase M2 modulation ascertained by lactate dehydrogenase coupled enzyme assay. The DFT studies highlighted the stability of the molecules.•Anticancer activity was confirmed by in vitro cytotoxicity studies in CAL 27 cell line.•The redox properties were investigated using cyclic voltammetry.•The surface properties were ascertained by FESEM and SC-XRD studies.•This study provides inspiration for synthesis of more such molecules acting as anticancer agents. We report the design and synthesis of fifteen novel ferrocene-based triazolopyrimidines and several other studies that establish these molecules as PKM2 modulators. Our ferrocene-based triazolopyrimidines (FTPs) were subjected to interaction with Pyruvate Kinase isoform, PKM2, which is vehemently overexpressed in oral, lung, breast, and colorectal cancers. The in silico outcomes and lactate dehydrogenase (LDH) coupled enzyme assay results revealed many of these molecules can be groomed into potential anticancer agents. Additionally, cyclic voltammetry disclosed that these species are redox-active, one of the criteria for metallocenes to act against cancer in general. Single-crystal X-Ray diffraction crystallography studies fully uncovered the 3D crystal lattice structure and their three-dimensional orientation in depth. Successively, in vitro cell viability studies were performed. Some compounds showed higher potency than cisplatin on CAL 27 cells representing human oral squamous cell carcinoma (OSCC). On top of that, these compounds turned out to be cancer-selective as the normal oral epithelial cell line was unaffected even at higher concentrations than the CAL 27 cell line. [Display omitted]