2. Academic Validation
  3. One- and Two-Photon Uncaging of Carbon Monoxide (CO) with Real-Time Monitoring: On-Demand Carbazole-Based Dual CO-Releasing Platform to Test over Single and Combinatorial Approaches for the Efficient Regression of Orthotopic Murine Melanoma In Vivo

One- and Two-Photon Uncaging of Carbon Monoxide (CO) with Real-Time Monitoring: On-Demand Carbazole-Based Dual CO-Releasing Platform to Test over Single and Combinatorial Approaches for the Efficient Regression of Orthotopic Murine Melanoma In Vivo

  • J Med Chem. 2022 Feb 10;65(3):1822-1834. doi: 10.1021/acs.jmedchem.1c00750.
Yarra Venkatesh 1,  Venugopal Vangala 2 3,  Rakesh Mengji 2 3,  Amrita Chaudhuri 1,  Sayantan Bhattacharya 4,  Prasanta Kumar Datta 4,  Rajkumar Banerjee 2 3,  Avijit Jana 2 5 3,  N D Pradeep Singh 1
Affiliations

Affiliations

  • 1 Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
  • 2 Department of Applied Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500007, India.
  • 3 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 4 Department of Physics, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
  • 5 Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500007, India.
PMID: 35019659 DOI: 10.1021/acs.jmedchem.1c00750
Abstract

Herein, we report three new metal-free, photochemically active single, dual, and combinatorial CORMs (photoCORMs) based on a carbazole-fused 1,3-dioxol-2-one moiety which released one equivalent of CO, two equivalent of CO, and a combination of one equivalent of each CO and Anticancer drug upon one- and two-photon excitation, respectively. The photoCORMs exhibited good cellular uptake and real-time monitoring ability of CO uncaging by a color change approach in cancerous B16F10 cells. Interestingly, the cytotoxicity assay on B16F10 cells indicated that the dual photoCORM has increased Anticancer activity over the single and combinatorial photoCORMs upon irradiation. Our results also showed that CO could accelerate the effectiveness of the well-known Anticancer drug (chlorambucil). Finally, the in vivo evaluation of the dual photoCORM on an established murine melanoma tumor (C57BL/6J mouse model) manifested a significant regression of tumor volume and led to significant improvement (>50%) in the overall survivability.

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