Design and synthesis of novel N(4)-substituted thiosemicarbazones bearing a pyrrole unit as potential anticancer agents

Abstract

Abstract.A series of N(4)-substituted thiosemicarbazones (TSCs) bearing pyrrole unit (1a-1e) were synthesized and fully characterized by elemental analyses, infrared spectra, 1 H nuclear magnetic resonance and single crystal X-ray diffraction. The compounds were assessed as potential chemotherapeutic agents. All newly synthesized compounds were screened for their anticancer activity against lung cancer PC-9, esophageal cancer Eca-109 and gastric cancer SGC-7901 cell lines. The results of MTT, Terminal deoxynucleotidyl transferase dUTP nick end labeling and fluorescence-activated cell sorting assays indicated that all the prepared compounds exhibited cytotoxicity against PC-9, Eca-109 and SGC-7901 cells in vitro. All the compounds significantly induced cancer cell apoptosis accompanied by increasing the Bax/Bcl-2 ratio and activation of caspase-3. The structure-activity association was discussed and the potential pre-clinical trials may be conducted. The present findings have a great potential in biomedical applications of novel N(4)-substituted TSCs.

Crystal structure of bis(N′-((5-(ethoxycarbonyl)-1H-pyrrol-2-yl)methylene)-N-ethylcarbamohydrazonothioato-κ2N,O)nickel(II), C22H30N8O4S2Ni

“…The four-coordinated Ni(II) ion is in a distorted square planar geometry with the donor sets of two N and two S atoms from two dependent TSC ligands. The length of C-S is 1.736(3) Å, which is much longer than that of 1.691(19) Å in the free molecule [6], showing that the TSC ligand has thiolated and deprotonated. Furthermore, the imine C=N (C8-N2) bond adopted a Z configuration instead of E in the free molecule [6].…”

“…The length of C-S is 1.736(3) Å, which is much longer than that of 1.691(19) Å in the free molecule [6], showing that the TSC ligand has thiolated and deprotonated. Furthermore, the imine C=N (C8-N2) bond adopted a Z configuration instead of E in the free molecule [6]. In the solid state, intermolecular N-H• • • O hydrogen bonds between the terminal amino N and carboxylate O atoms link molecules into a two-dimensional supermolecular network.…”

“…Thiosemicarbazones (TSCs) and their transition metal complexes have attracted attention in the coordination chemistry because of their high biological and pharmaceutical activities, such as antibacterial, antiviral, antifungal, antitumor activity and so on [3,4]. It is noted that N(4)-substituted TSCs bearing pyrrole units could act as potential chemotherapeutic agents [5,6]. Herein, the title Ni(II) complex with a pyrrole-TSC ligand is reported, which was synthesized and characterized by X-ray diffraction.…”

Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

“…Some studies showed that pyrrole unite containing compounds have antitumor activity (Vine et al., 2009), so a series of N (4)‐substituted thiosemicarbazones bearing a pyrrole unit were assessed as potential chemotherapeutic agent (Huang et al., 2010). Zhu et al., (2017) synthesized five compounds and characterized by spectroscopic techniques. The synthesized compounds were assayed for cytotoxicities against SGC −7901 (gastric), PC‐9 (lung), and Eva 109 (esophageal) cancer cell lines.…”

The BIOLOGICAL EFFICACY OF MIXED LIGAND COPPER(II) COMPLEXES OF N(4)-SUBSTITUTED THIOSEMICARBAZONE AND DIIMINE CO-LIGANDS AS CHELATING N, N’- DONOR LIGAND

“…Significantly, the biological properties of thiosemicarbazone compounds are comparatively higher than that of the other transition metal complexes probably due to the synergic effect among thiosemicarbazone ligands and the presence of central metal ion [6]. Recently, Zhu et al found that potential biological properties of novel N(4)-substituted thiosemicarbazide with pyrrole moiety against PC-9, Eca-109, and SGC-7901 cell lines [7]. Moreover, the substituted thiosemicarbazone at N(4) position did not show any effect on the geometry of the complexes, but it influences the biological activity of the corresponding complexes and shows significant activity.…”