Investigations on Anticancer Potentials by DNA Binding and Cytotoxicity Studies for Newly Synthesized and Characterized Imidazolidine and Thiazolidine-Based Isatin Derivatives

Abstract

Imidazolidine and thiazolidine-based isatin derivatives (IST-01–04) were synthesized, characterized, and tested for their interactions with ds-DNA. Theoretical and experimental findings showed good compatibility and indicated compound–DNA binding by mixed mode of interactions. The evaluated binding parameters, i.e., binding constant (Kb), free energy change (ΔG), and binding site sizes (n), inferred comparatively greater and more spontaneous binding interactions of IST-02 and then IST-04 with the DNA, among all compounds tested under physiological pH and temperature (7.4, 37 °C). The cytotoxic activity of all compounds was assessed against HeLa (cervical carcinoma), MCF-7 (breast carcinoma), and HuH-7 (liver carcinoma), as well as normal HEK-293 (human embryonic kidney) cell lines. Among all compounds, IST-02 and 04 were found to be cytotoxic against HuH-7 cell lines with percentage cell toxicity of 75% and 66%, respectively, at 500 ng/µL dosage. Moreover, HEK-293 cells exhibit tolerance to the increasing drug concentration, suggesting these two compounds are less cytotoxic against normal cell lines compared to cancer cell lines. Hence, both DNA binding and cytotoxicity studies proved imidazolidine (IST-02) and thiazolidine (IST-04)-based isatin derivatives as potent anticancer drug candidates among which imidazolidine (IST-02) is comparatively the more promising.

Augmented anticancer effect and antibacterial activity of silver nanoparticles synthesized by using Taxus wallichiana leaf extract

“…U251 cells, derived from a human malignant glioblastoma multiforme (GBM) were incubated with MTT (3-[4,5- dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (Sigma Aldrich, St. Louis, MO, USA) and 1% penicillin/streptomycin in Dulbecco modified eagle media (DMEM) containing extra glucose and 10% Fetal Bovine Serum (FBS; Thermo Fischer Scientific, Waltham, MA, USA). Cells were maintained and upon reaching 90 percent confluence, trypsinised and sub cultured until needed for MTT assay ( Arshad et al, 2022 ).…”

Structure and surface analyses of a newly synthesized acyl thiourea derivative along with its in silico and in vitro investigations for RNR, DNA binding, urease inhibition and radical scavenging activities

“…43 Computational approach not only helpful for the validation of experimental ndings for compoundprotein/or DNA binding interactions but may support to divulge the candidacy of a compound as potent anticancer drug. [44][45][46][47] Ribonucleotide reductase (RNR) plays important role in de novo synthesis of DNA precursors by catalyzing reduction of ribonucleotide in their respective deoxy ribonucleotide. RNR from higher organisms consists of two dimers i.e., R1 and R2.…”

“…50 Using the absorbance of (4), before (A o ) and aer DNA additions (A), in the Hildebrand eqn (2), K b (binding constant) was evaluated and further used to calculate DG (Gibbs free energy change) from Van't hoff eqn (3). 37,39,40,42,[44][45][46][47]50,51…”

“…The negative value of DG indicated the binding spontaneity while the evaluated magnitude of binding constant in current studies for (4)-DNA binding has been reported for both intercalation and groove binding interaction. [44][45][46][47][50][51][52][53][54] The spectral variations and related binding parameters exhibited that the compound (4) interacted with DNA via weak interaction that was most probably occur via intercalation/or groove binding. However, insignicant peak shiing in (4)-DNA spectra and docking analysis identied compound (4) as groove binder.…”

Tryptophan Metabolites as Mediators of Microbiota-Gut-Brain Communication: Focus on Isatin

“…Although isatin analogs may effectively interact with DNA in vitro (e.g., Arshad et al, 2022 ), the effect of isatin on gene expression is obviously mediated by various nucleoproteins, including histones and histone modifying enzymes (e.g., histone deacetylase) ( Medvedev et al, 2018 ; Hua et al, 2021 ).…”