2,2'-Bipyridine-Modified Tamoxifen: A Versatile Vector for Molybdacarboranes

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Cancer Research

Background:

• Antitumor activity of metallacarboranes is underexplored, with limited studies on ruthena- and molybdacarboranes.
• Tamoxifen (TAM-diOH) is a well-established drug, providing a basis for designing novel therapeutic agents.

Purpose of the Study:

• To synthesize and evaluate the antitumor potential of a novel molybdacarborane derivative linked to a tamoxifen-inspired moiety.
• To investigate the cytotoxic effects and cellular mechanisms of the synthesized compounds against various cancer cell lines.

Main Methods:

• Synthesis of a molybdacarborane derivative ([3,3-{4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2'-bipyridine-κ2 N,N'}-3-(CO)2 -closo-3,1,2-MoC2 B9 H11 ] (10)) and its ligand (4-[1,1-bis(4-hydroxyphenyl)but-1-en-2-yl]-2,2'-bipyridine (6)).
• Assessment of cytotoxic activities against breast adenocarcinoma (MDA-MB-231, MDA-MB-361, MCF-7), human glioblastoma (LN-229), and human glioma (U-251) cell lines.
• Evaluation of compound-induced senescence, autophagy, reactive oxygen/nitrogen species (ROS/RNS) levels, and nitric oxide (NO) production.

Main Results:

• Compounds 6 and 10 demonstrated cytotoxic effects in the low micromolar range against all tested cancer cell lines.
• Both compounds induced senescence and cytodestructive autophagy.
• Compounds 6 and 10 reduced ROS/RNS levels, while compound 10 significantly increased nitric oxide (NO) concentration in MCF-7 cells.

Conclusions:

• The novel molybdacarborane derivative (10) and its ligand (6) exhibit significant cytotoxic and antiproliferative activities.
• These compounds represent a promising new class of metallacarboranes for cancer therapy, with distinct mechanisms of action including induction of senescence and autophagy.
• Further investigation into the therapeutic potential of these compounds is warranted.