Investigations on the Anticancer Potential of Benzothiazole-Based Metallacycles

Abstract

A series of 2-phenylbenzothiazole derivatives and their corresponding organometallic ruthenium(II) and osmium(II) complexes were synthesized, designed to exploit both, the attributes of the half-sandwich transition metal scaffold and the bioactivity spectrum of the applied 2-phenylbenzothiazoles. All synthesized compounds were characterized via standard analytical methods. The obtained organometallics showed antiproliferative activity in the low µM range and are thus at least an order of magnitude more potent than the free ligands. ESI-MS measurements showed that the examined compounds were stable in aqueous solution over 48 h. Additionally, their binding preferences to small biomolecules, their cellular accumulation and capacity of inducing apoptosis/necrosis were investigated. Based on the fluorescence properties of the selected ligand and the corresponding ruthenium complex, their subcellular distribution was studied by fluorescence microscopy, revealing a high degree of colocalization with acidic organelles of cancer cells.

Investigating the anticancer potential of 4-phenylthiazole derived Ru(ii) and Os(ii) metalacycles

“…A similar trend was observed with the related 4-phenyltriazole based Ru(II)and Os(II)-arene compounds by Riedl et al 15 The metal-chlorido bond lengths (2.4124(11)-2.4232(6) Å) are consistent with anticipated values. 15,25,[34][35][36]…”

“…The chloride-ion affinity of 2a and 2c was investigated via UV-Vis spectroscopy at various KCl concentrations at 25 °C…”

“…24 Consequently, scientists emphasized alternatives with improved stability under physiological conditions, which led us to the investigation of C,N-coordination motifs in bidentate ligands for cytotoxic organometallics. 15,17,25 Over the last years, especially C,N-coordinated Ru(II) metalacycles featuring 2-arylthiazole, 26 2-phenylindole, 27 2-phenylpyridin, 28 benzimidazole, 29,30 4-phenyltriazole 15,17 and 2-phenylben-zothiazole 25 scaffolds have been reported. In contrast, the biological properties and the cytotoxicity of osma(II)cycles of the general form [Os(arene)L CΛN Cl] remain nearly unexplored and were only investigated by Boff et al, 31 Riedl et al 15 and Mokesch et al 25 In every case, promising cytotoxicities in the low micromolar range were reported.…”

A Novel Class of Potent Anti-Tyrosinase Compounds with Antioxidant Activity, 2-(Substituted phenyl)-5-(trifluoromethyl)benzo[d]thiazoles: In Vitro and In Silico Insights

“…Compound 1a has a benzothiazole ring, which is analogous to other compounds with a 5-membered ring fused to benzene, such as indoles, benzimidazoles, benzofurans, and benzothiophenes, and these structures are widely used by medicinal chemists as scaffolds. Studies have shown that 2-arylbenzothiazole derivatives have diverse biological activities [ 23 ], such as antibacterial [ 24 , 25 , 26 ], anticancer [ 27 , 28 , 29 , 30 ], antioxidant [ 31 ], anti-tuberculosis [ 32 ], neuroprotective [ 33 ], hyaluronidase inhibitory [ 34 ], and antifungal properties [ 35 ]. In addition, the 2-arylbenzothiazole scaffold is found in various drugs, such as zopolrestat, pramipexole, ethoxazolamide, and entaluron.…”

“…Studies have shown that 2-arylbenzothiazole derivatives have diverse biological activities [23], such as antibacterial [24][25][26], anticancer [27][28][29][30], antioxidant [31], anti-tuberculosis [32], neuroprotective [33], hyaluronidase inhibitory [34], and antifungal properties [35]. We synthesized a series of 16 derivatives of compound 1a and examined their tyrosinase inhibitory activities using mushroom and murine cellular tyrosinase, and their antimelanogenic effects in murine B16F10 cells.…”