Pt(II) Bis(pyrrole-imine) complexes: Luminescent probes and cytotoxicity in MCF-7 cells†.

Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal structure of 2,2'-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis(pyrrol-1-ido)platinum(II) (1) was obtained. Pt(II) complexes 1-4 exhibited phosphorescence, with increased luminescence in anaerobic solvents or when bound to human serum albumin (HSA). One of the complexes shows a 15.6-fold increase in quantum yield when bound to HSA and could be used to detect HSA concentrations as low as 5 nM. Pt(II) complexes 1-3 was investigated as potential theranostic agents in MCF-7 breast cancer cells, but only complex 3 exhibited cytotoxicity when irradiated with UV light (λ355nmExcitation). Interestingly, the cytotoxicity of complex 1 was unresponsive to UV light irradiation. This indicates that only complex 3 can be considered a potential photosensitising agent.

Design, Synthesis, Antiproliferative Evaluation, and Molecular Docking Studies of N-(3-Hydroxyindole)-Appended ß-Carbolines/Tetrahydro-ß-Carbolines Targeting Triple-Negative and Non-Triple-Negative Breast Cancer.

The present manuscript pertains to the design and synthesis of a series of 3-hydroxyindole-substituted ß-carbolines/tetrahydro-ß-carbolines with an aim to explore their antiproliferative structure-activity relationship against breast cancer. The conjugate with an optimum combination of a flexible tetrahydro-ß-carboline core, a tertiary alcoholic group along with a chloro substituent on the indole ring, proved to be the most active compound. It displayed IC50 values of 13.61 and 22.76 µM against MCF-7 (ER+) and MDA-MB-231 (ER-) cells, respectively. The docking studies were found to be consistent with experimental results owing to the stronger binding affinity of the synthesized conjugates via hydrophobic and H-bonding interactions.

Triarylethylene-indolin-2,3-dione molecular conjugates: design, synthesis, docking studies and anti-proliferation evaluation.

A series of 1H-1,2,3-triazole-linked ospemifene-isatin and O-methylated ospemifene-isatin conjugates were synthesized and assayed for their anti-proliferative activities against estrogen-responsive as well as estrogen-non-responsive cells. The non-cytotoxic conjugate 14e, with an optimal combination of bromo substituents at the C-5/C-7 positions of isatin, proved to be a promising hit with an IC50 value of 31.62 µM against MCF-7 and 19.23 µM against MDA-MB-231. The observed anti-proliferative activities of active conjugates were further corroborated via docking studies carried out on estrogen receptor subtypes α and ß.

1H-1,2,3-Triazole Tethered Nitroimidazole-Isatin Conjugates: Synthesis, Docking, and Anti-Proliferative Evaluation against Breast Cancer.

1H-1,2,3-Triazole tethered imidazole-isatin and imidazole-isatin-thiosemicarbazone conjugates were synthesized and evaluated against MCF-7 and MDA-MB-231 cell lines. Antiproliferative activities of the synthesized conjugates revealed an optimum combination of longer alkyl chain length as spacer and a halogen-substituent on the isatin ring as a pre-requisite for good activity. The compound 6g with an optimum combination of chloro-substituent at C-5 position of isatin ring and a butyl chain length proved to be most active and noncytotoxic with IC50s of 54.25 and 26.12 µM against MCF-7 and MDA-MB-231 cell lines, respectively.

Azide-Alkyne Cycloaddition En Route to 1H-1,2,3-Triazole-Tethered Isatin-Ferrocene, Ferrocenylmethoxy-Isatin, and Isatin-Ferrocenylchalcone Conjugates: Synthesis and Antiproliferative Evaluation.

Diverse series of isatin-ferrocene conjugates were synthesized via Cu-promoted azide-alkyne cycloaddition reaction with an aim of probing their antiproliferative structure-activity relationship against MCF-7 (estrogen receptor positive) and MDA-MB-231 (triple negative) cell lines. Among the synthesized conjugates, isatin-ferrocenes proved to be more potent against MCF-7, whereas ferrocenylmethoxy-isatins exhibited activity against MDA-MB-231 cell lines. However, the introduction of chalcone moiety among these hybrids resulted in the complete loss of activity against the tested cell lines, as evident by isatin-ferrocenylchalcones. The conjugates 5a and 9c proved to be the most potent among the series against MCF-7 and MDA-MB-213 cell lines, exhibiting IC50 values of 31.62 and 20.26 µM, respectively.