Аннотация:A class of cyclometalated RhIII complexes [Cp*Rh(ppy)(SR)] bearing thiolate ligands, Cp* =pentamethylcyclopentadienyl, ppy = 2-phenylpyridinate and R = pyridyl (Spy, 2), pyrimidyl(SpyN, 3), benzimidazolyl (Sbi, 4), benzothiazolyl (Sbt, 5), were produced and were identified bymeans of spectroscopy methods. The in vitro cytotoxicity of the RhIII compounds versus of threedifferent human mortal cancerous cells (ovarian, SKOV3; breast, MCF-7; lung, A549) and anormal and non-tumorigenic lung (MRC-5) cell line were evaluated, indicating the selectivity ofthese cyclometalated RhIII complexes to cancer cells. Complex 5 selected for in vivo experimenthas shown an effective inhibition of tumor growth in SKOV3 xenograft mouse model relative tocontrol (pValue < 0.05 and < 0.01). Importantly, the outcomes of H&E (hematoxylin and eosin)staining and hematological analysis revealed negligible toxicity of 5 compared to cisplatin on afunction of the main organs of mouse. Molecular docking, UV-vis and emission spectroscopies(fluorescence, 3D fluorescence, synchronous) techniques were performed on 1‒5 to peruse themechanism of the anticancer activities of these complexes. The obtained data help to manifestbinding affinity between the rhodium compounds and CT-DNA (calf thymus DNA) through theinteraction by DNA minor groove and moderate binding affinity with BSA (bovine serumalbumin), particularly with the cavity in the subdomain IIA. It can be concluded that the Rhthiolate complexes are highly promising leads for the development of novel effective DNAtargeted anticancer drugs.