Browsing by Author "Rajesh Kumar Kushwaha"

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A bexarotene-attached Re(i) tricarbonyl complex for NADH oxidation and ROS-mediated cancer phototherapy
(Royal Society of Chemistry, 2025) Rajesh Kumar Kushwaha; Virendra Pratap Singh; Biplob Koch; Samya Banerjee
An axially substituted polypyridyl Re(CO)3 complex bearing bexarotene triggered caspase-3/7-mediated apoptosis in cancer cells through ROS generation and NADH photo-oxidation. © 2025 The Royal Society of Chemistry.
Anticancer potential of polypyridyl-based Ir(III)-coumarin 6 conjugates under visible light and dark
(Elsevier B.V., 2025) Ashish Kumar Kumar Yadav; Virendra Pratap Singh; Rajesh Kumar Kushwaha; Amit Kunwar; Biplob Koch; Samya Banerjee
We developed and evaluated two novel coumarin 6 conjugated Ir(III) photocatalysts, [Ir(CO6)(Ph-tpy)Cl]Cl (Ir1) and [Ir(CO6)(An-tpy)Cl]Cl (Ir2) (CO6 = Coumarin 6, Ph-tpy = 4′-phenyl-2,2′:6′,2″-terpyridine, An-tpy = 4′-anthracenyl-2,2′:6′,2″-terpyridine), for application in cancer therapy. Upon green light irradiation (525 nm, 50.2 J cm−2), Ir1 and Ir2 effectively catalyzed NADH oxidation with turnover frequencies (TOFs) ranging from 840 to 1100 h−1 in phosphate-buffered saline. Additionally, these complexes generated reactive oxygen species (ROS), including 1O2 and [rad]OH, through type I and type II mechanisms. Ir1 and Ir2 exhibited significant toxicity against human breast (MCF-7) and cervical (HeLa) cancer cells, with Ir2 demonstrating enhanced anticancer activity upon light activation. Notably, both complexes showed minimal dark toxicity toward non-cancerous human embryonic kidney (HEK-293) cells. The selectivity index (SI = Dark IC50 in normal cells/Dark IC50 in cancer cells) for Ir1 and Ir2 reached up to 22, highlighting their preferential activity in cancer cells. Mechanistic studies in MCF-7 cells with the most effective complex, Ir2, revealed that light exposure increased ROS production and induced mitochondrial depolarization and apoptosis via caspase 3/7 activation. © 2025 Elsevier B.V.
Sonodynamic Cancer Therapy by Mn(I)-tricarbonyl Complexes via Ultrasound-triggered CO Release and ROS Generation
(John Wiley and Sons Inc, 2025) Ashish Kumar Kumar Yadav; Virendra Pratap Singh; Sagar Acharjee; Sukanta Saha; Rajesh Kumar Kushwaha; Arnab Dutta; Biplob Koch; Samya Banerjee
A novel ferrocene conjugated Mn(I)-tricarbonyl complex viz [Mn(Fc-tpy)(CO)3Br] (Mn2) where, Fc-tpy=4′-ferrocenyl-2,2′:6′,2′′-terpyridine was synthesized and fully characterized along with its non-ferrocene analog [Mn(Ph-tpy)(CO)3Br] Ph-tpy=4′-phenyl-2,2′:6′,2′′-terpyridine (Mn1) for ultrasound (US) activated anticancer applications. The X-ray structure of Mn2 confirmed its distorted octahedral geometry. Mn1 and Mn2, for the first time, showed US-triggered release of CO and ROS generation (1O2 and ⋅OH) in an aqueous solution from any Mn(I)-tricarbonyl complexes, indicating its potential for synergetic CO gas therapy and sonodynamic therapy. The above-mentioned in-solution chemistry was successfully translated into in vitro cellular models. These complexes showed unprecedented US-triggered toxicity against T-cell lymphoma and human breast cancer cells (IC50 for Mn2<1 μM) while were minimally toxic without US or against normal spleen and human embryonic kidney cells. Mn2 was ca. 12 fold more anticancer active than Mn1, indicating that the ferrocene conjugation augmented the US sensitivity. The apoptotic sonotoxicity of Mn2 was due to US-promoted mitochondrial depolarization via ROS generation and CO release. The apoptosis was triggered by caspase 3 activation. This is the first report of Mn(I)-tricarbonyl-based sonosensitizers for cancer SDT. Overall, this study, for the first time, establishes the effectiveness of 3d metal carbonyls in SDT. © 2024 Wiley-VCH GmbH.