University of Johannesburg
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Triazolyl RuII, RhIII, OsII, and IrIII Complexes as Potential Anticancer Agents: Synthesis, Structure Elucidation, Cytotoxicity, and DNA Model Interaction Studies. Organometallics, 2019

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posted on 2020-05-05, 08:10 authored by Charles K. Rono,, William K. Chu, James Darkwa, Debra Meyer, Banothile C. E. Makhubela
Novel conjugated ruthenium(II), rhodium-
(III), and iridium(III) organometallic complexes of triazoles
1 and 2 synthesized and evaluated for anticancer activity
against cervical (HeLa), kidney (HEK293), nonsmall lung
cancer (A549), and leukemia (MT4) cancer cell lines are
reported herein. The complexes are κ2-N,C coordinated and
have the formula [ML(Ar)Cl] (where L is 1-benzyl-4-phenyl-
1H-1,2,3-triazole for 1 and 1-benzyl-4-hydroxymethyl-1H-
1,2,3-triazole for 2, Ar is p-cymene for RuII and OsII and Cp*
for RhIII and IrIII, and M is metal). NMR studies, including
HMBC and NOESY, were employed to unambiguously
elucidate their structures and provide their conformational information in solution. Single-crystal X-ray diffraction data have
been used to establish the solid-state structures of selected complexes, which further confirm the structural elucidation by NMR.
Dynamic NMR studies, such as differential transferred NOE, have been employed to distinguish between isomers 1a_I and
1a_II of ruthenium(II) complexes of triazole 1. The rhodium(III) (1b) and iridium(III) (1c) complexes exhibited good
cytotoxic activities (CC50 = 4−6 μM) comparable to that of the drug auranofin against lung cancer A549 cell lines (CC50 = 4.69
μM). While triazole 1 based ruthenium(II) (1a) and osmium(II) (1d) complexes displayed modest anticancer activities against
HeLa and HEK293 cell lines, the analogous rhodium(III) and iridium(III) complexes exhibited good potential (CC50 = 9−54
μM versus auranofin (3−9 μM)) against these cancer cell lines. Insightful NMR studies on the interaction between the DNA
model guanosine 5′-GMP and the complexes 1b,c reveal a possible mode of action of the aquated complexes involving
carbenylation with DNA bases or purines through the triazolyl proton H-5. From the findings, these complexes could possibly
confer their cytotoxic activities through intercalation with the DNA of pathological cells. Therefore, carbenylation of the
triazolylrhodium(III) and iridium(III) complexes by DNA guanosine 5′-GMP is proposed as a novel mode of DNA
intercalation of these complexes in cancer cells.


TWAS in partnership with the South African National Research Foundation (Grant Nos. 99992, 95517, and 99269)


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