Novel isothiacalothrixin B analogues exhibit cytotoxic activity on human colon cancer cells in vitro by inducing irreversible DNA damage

Abstract

Preliminary cytotoxic analysis of sulphur containing isosteric analogues of calothrixin B identified the useful anti-tumour activity of thia/isothiacalothrixin B which necessitated it’s biological evaluation in colon and lung cancer cell lines. The isothia analogues induced cytotoxicity of HCT116 in a time-dependent manner and inhibited the clonogenic survival of HCT116 and NCI-H460 cells in a dose-dependent manner comparable to the standard anti-cancer drug camptothecin. Herein employing flow cytometry, we demonstrate that isothiacalothrixin B analogues inhibited proliferation of colon cancer cells by the arrest of cells in S and G2/M phases over a period of 48 hours at a concentration of 5 μM. Our results also suggest that the cytotoxicity of thia analogues of calothrixin B is partially mediated by induction of cellular DNA strand breaks. The UV-Vis spectroscopic studies with CT-DNA revealed groove binding for calothrixin B and its thia analogues wherein subsequent in silico molecular modelling studies indicated preferential binding to the AT-rich regions of minor groove of DNA. Furthermore, thiacalothrixin B caused transcriptional activation of p21waf1/cip1 promoter and upregulation of its protein levels independent of p53. The induction of DNA damage response pathway leads to apoptosis in isothiacalothrixin B but not in thiacalothrixin B treated cells. The isothia analogues SCAB 4 induced DNA strand breaks and cell cycle arrest even after treatment for a short period (i.e., 4 hours) and the cell cycle effects were irreversible. For the first time, this study provides detailed cellular effects on the potential use of isothiacalothrixin B analogues as cytotoxic agents.

Non‐Covalent Interactions in the Self‐Assembly of Dihydropyridone Supramolecules and In Vitro Anti‐Cancer Assessment in Human Lung Adenocarcinoma Cell Line (A549)

“…Treatment of cancer cells with different doses (50–150 μM) of compound 2 for 24 induced significant DNA damage in A549 cells in a dose‐dependent manner as indicated by the increased tail intensity, tail length, tail DNA, tail moment, and olive moment (Figure 12(A) and (B)). Several anti‐cancer drugs have also shown similar effects in various cancer types [33–36] …”

Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4‐Ethylenedioxythiophenyl‐2‐propen‐1‐one Analogues

“…Clonogenic cell survival assay : Clonogenic assays were performed on HCT116 and NCI‐H460 cells according to the reported procedure . In brief, EDOT analogues at different concentrations were incubated with cells seeded at a very low density (100 cells per well of a six‐well plate), followed by washing with Dulbecco′s phosphate‐buffered saline (DPBS) and culturing the drug‐treated cells for a further 12 days in DMEM culture medium.…”

Synthesis, anticancer evaluation of novel hybrid pyrazole-based chalcones, molecular docking, DNA fragmentation, and gene expression: in vitro studies

“…These interactions include a pi donor hydrogen bond between GLU 12 and thiophene moiety (5.88 Å), an ionic bond between GLU 8 and nitrogen atom of nitrophenol moiety (5.28 Å). [36][37][38][39][40] In addition to three alkyl interactions between methylchloro-imidazole moiety ILE 10 and LEU 134 amino acid residues (5.03, 5.04, 5.18 Å). Five pi-alkyl interactions with VALA 18, ALA 144, ILE 10, LEU 134, HIS 82 (5.80, 6.49, 4.87, 5.89, 4.85 Å) (Fig.…”