Despite phenomenal clinical success, the efficacy of platinum anticancer drugs is often compromised due to inherent and acquired drug resistant phenotypes in cancers. To circumvent this issue, we designed two heterobimetallic platinum (II)‐ferrocene hybrids that display multi‐pronged anticancer action. In cancer cells, our best compound, 2, platinates DNA, produces reactive oxygen species, and has nucleus, mitochondria, and endoplasmic reticulum as potential targets. The multi‐modal mechanism of action of these hybrid agents lead to non‐apoptotic cell death induction which enables circumventing apoptosis resistance and significant improvement in platinum cross resistance profile. Finally, in addition to describing detail mechanistic insights, we also assessed its stability in plasma and demonstrate anticancer efficacy in an in vivo A2780 xenograft model. Strikingly, compared to oxaliplatin, our compound displays better tolerability, safety profile and efficacy in vivo.

Emergence of resistance in cancer cells and dose-limiting side effects severely limit the widespread use of platinum (Pt) anticancer drugs. Multiaction hybrid anticancer agents that are constructed by merging two or more pharmacophores offer the prospect of circumventing issues of Pt drugs. Herein, we report the design, synthesis, and in-depth biological evaluation of a ruthenium− ferrocene (Ru-Fc) bimetallic agent [(η 6 -p-cymene)Ru(1,1,1-trifluoro-4-oxo-4ferrocenyl-but-2-en-2-olate)Cl] and its five analogues. Along with aquation/ anation chemistry, we evaluated the in vitro antitumor potency, Pt cross-resistance profile, and in vivo antiangiogenic properties. A structure activity analysis was performed to understand the impact of Fc, CF 3 , and p-cymene groups on the anticancer potency of the Ru-Fc hybrid. Finally, in addition to assessing cellular uptake and intracellular distribution, we demonstrated that the Ru-Fc hybrid binds to nucleophilic biomolecules and produces reactive oxygen species, which causes mitochondrial dysfunction and induces ER stress, leading to poly(ADP−ribose) polymerasemediated necroptotic cell death.

The BOPHY based organotellurium containing probe was synthesized and characterized with single crystal XRD for selective and sensitive detection of Hg2+ over other metal ions. The probe detects Hg2+ in...

First organoselenium containing BOPPY based small molecular probe was synthesized and the structure was elucidated by NMR and single-crystal X-ray diffraction. The probe have high selectivity and sensitivity towards hypochlorite...

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