A Nine-Coordinated Bismuth(III) Complex Derived from Pentadentate 2,6-Diacetylpyridine Bis(⁴N-methylthiosemicarbazone): Crystal Structure and Both in Vitro and in Vivo Biological Evaluation

Abstract

Up to now, bismuth(III) complexes with thiosemicarbazones have been comparatively rare. Few in vivo biological studies have been carried out in comparison to the plentiful in vitro data. Here, an interesting nine-coordinated bismuth(III) complex, [Bi(H2L)(NO3)2]NO3 [1; H2L = 2,6-diacetylpyridine bis((4)N-methylthiosemicarbazone)], has been synthesized and structurally characterized. The analytical data reveal the formation of 1:1 (metal/ligand) stoichiometry. In vitro biological studies have indicated that the bismuth complex 1 has shown much higher antibacterial and anticancer activities than its parent ligand, especially with MIC = 10.66 μM against Bacillus cereus and Salmonella typhimurium and IC50 = 26.8 μM against K562 leukemia cells, respectively. More importantly, it also evidently inhibits H22 xenograft tumor growth on tumor-bearing mice (10 mg/kg; inhibitory rate = 61.6%). These results indicate that coordination to bismuth(III) might be an interesting strategy in the discovery of new anticancer drug candidates.

Synthesis, structure investigation and biological evaluation of 2-thiophene N(4)-phenylthiosemicarbazone and its three metal derivatives

“…In recent years, we have been working on the structural and biological properties of thiosemicarbazones and their metal complexes [17,21,25,[27][28][29][30][31][32][33]. We focus our mind on the optimization of thiosemicarbazones and the selective preference of metal ions in order to effectively enhance biological activities and reduce the potential toxicity.…”

Review: Bismuth complexes: synthesis and applications in biomedicine

“…For example, a new bismuth(III)-sulfapyridine complex was synthesized by Marzano and co-workers, which inhibited the growth of chronic myelogenous leukemia cells with an IC 50 value of 44 μM, implying more potent anticancer effects than the free ligand [71]. A nine-coordinate bismuth(III) complex derived from pentadentate 2,6-diacetylpyridine bis ( 4 N-methylthiosemicarbazone) was first synthesized by Li et al [22] and showed much higher antibacterial and anticancer activities than its parent ligand during in vitro biological studies, especially with MIC = 10.66 μM against Bacillus cereus and S. typhimurium and IC 50 = 26.8 μM against K562 leukemia cells. It also evidently inhibited H22 xenograft tumor growth on tumor-bearing mice.…”

Synthesis, Crystal Structures, and Cytotoxicity of Thiophene-2-carbaldehyde N(4)-Cyclohexylthiosemicarbazone and Its Diorganotin(IV) Complex

“…[1][2][3][4][5][6][7] Triapine, a very good case in point, has been tested in phase I trial for patients with advanced solid tumors. [8] The biological activities of thiosemicarbazones often show a high dependence on their substituents.…”

“…[3,4,9,16,19,20] The results have revealed that heterocyclic thiosemicarbazones and their metal complexes show significant biological activities. After a careful literature search, we can affirm that thiophene-2-carbaldehyde N(4)-substituted thiosemicarbazones and their diorganotin(IV) complexes are scarce.…”