Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

Abstract

Synthesized and characterized a series of rhenium(I) trycarbonyl-based complexes with increased lipophilicity. Two of these novel compounds were discovered to possess remarkable anticancer, anti-angiogenic and antimetastatic activity <i>in vivo</i> (zebrafish-human CRC xenograft model), being effective at very low doses (1-3 µM). At doses as high as 250 µM the complexes did not provoke toxicity issues encountered in clinical anticancer drugs (cardio-, hepato-, and myelotoxicity). The two compounds exceed the antiproliferative and anti-angiogenic potency of clinical drugs cisplatin and sunitinib-malate, and display a large therapeutic window.

Metal Complexes in Cancer Treatment: Journey So Far

“…Compound 93 was the most effective on all the examined cancer cell lines, except HCT-116 cell lines. [148] Suntharalingam et al (2014) synthesized rhenium oxo complexes (Figure 50). They evaluated them for anticancer activity on a panel of NTERA-2 (carcinoma), U2OS (bone), HeLa, A549 (lung), A2780 and A2780CP70 (ovarian), and MRC-5 (liver) cancer cell lines as shown in (Table 50).…”

Synthesis, characterisation and biological evaluation of monometallic Re(i) and heterobimetallic Re(i)/Fe(ii) complexes with a 1,2,3-triazolyl pyridine chelating moiety

“…In the zebrafish xenograft model of colorectal carcinoma, the complexes inhibited tumor growth, vascularisation and tumor cell metastasis without inducing cardio-, hepato-, and myelotoxicity. 35 A series of water-coordinated Re(I) complexes proved effective against cervical carcinoma (HeLa), several wild-type and cisplatin-resistant cell lines, with the 2,9dimethyl-1,10-phenanthroline complex IX being the most active, and were also less toxic to human fibroblast cells compared with cisplatin. 36 There is increasing interest in the development of bi-, triand polydentate ligand architectures incorporating 1,2,3-triazolyl-based donor ligands 37,38 that can coordinate metals at the N-3, N-2 and C-5 donor sites.…”