PC-3 Carcinoma Cell Lines Research Articles

Bioinspired thiazolo-[2,3-b] quinazolin-6-one derivatives as potent anti-cancer agents targeting EGFR: their biological evaluations and in silico assessment.

Cancer is a challenging and second most deadly disease. The epidermal growth factor receptors (EGFRs) dimerize upon ligand bindings to the extracellular domain that intiates the downstream signaling cascades and activates intracellular kinase domain. Thus, activation of autophosphrylation through kinase domain results in metastasis, cell proliferation, and angiogenesis. In this study, we unravel the binding mechanism of newly synthesized thiazolo-[2,3-b] quinazolin-6-one and evaluate their anti-cancer activity against ovary and prostate carcinoma cell lines (OVCAR-3 and PC-3). Synthesized molecules exhibited promising anti-cancer activity against OVCAR-3 and PC-3 carcinoma cell lines with inhibitory concentrations ranging from 13.4 ± 0.43 to 23.6 ± 1.22μM and 7.5 ± 0.62 to 67.5 ± 1.24μM, respectively. These compounds induced apoptosis and resulted in cell cycle arrest at G1 and G2/M transition phases. Next, the nude mice models were taken to investigate the toxicity of the 4bi compound, and in vivo investigations revealed no effects upon examined organs (liver and kidney) treated at different concentrations. Moreover, the combined in silico approaches, molecular docking, molecular dynamics simulations, and MM/PBSA methods were performed to assess the binding affinity and stability of bioinspired synthesized congeners with the epidermal growth factor receptor tyrosine kinase (EGFR-TK). The free binding energy (ΔGbind) of the 4bi molecule was found comparable to Erlotinib drug. The test molecule could be competent for further usage to determine its efficicacy in cancer therapeutics.

Synthesis and characterization for pharmaceutical models from Co(II), Ni(II) and Cu(II)-thiophene complexes; apoptosis, various theoretical studies and pharmacophore modeling

New Co(II), Ni(II) and Cu(II) complexes were prepared from thiophene derivative and then characterized to elucidate their chemical formulae. IR-spectral data suggested a monobasic tridentate binding mode for the ligand towards the metal ions within mono-nuclear complexes. Ligand filed transitions as well as magnetic susceptibility, orient strongly for square-planer geometry with Ni(II) and Cu(II) complexes, while octahedral geometry for Co(II) complex. Mass spectroscopy and TGA were performed for complexes to assess on their molecular formulae and the molecular ion peak is attributing to dehydrating complex (M+-nH2O). TEM, EDX and XRD were carried out to indicate morphology, crystallinity and chemical composition of tested complexes. The crystal data estimated, reflect nanometer sizes of studied complexes. DFT method was utilized to obtain optimized structures under 6-31G and LANL2DZ basis sets. Hirshfeld surface properties were estimated for 3D crystal models of complexes, to put view about the contact strength within crystal packing. 2D-fingerprint plots for elemental contribution, clarify the effective contribution of O and H atoms in surface contact between crystals. Cu (II) complex showed greatest potent cytotoxic profile against MCF-7, HepG2 and PC-3 carcinoma cell lines, by IC50s 2.2, 2.6 and 2.1 μg, respectively. High killing rate for tumor cells was observed with an early apoptotic pathway under treatment with all compounds. Also, Cu(II) complex stimulates necrosis killing effect on prostate (PC-3) and breast (MCF-7) cancer cells. Ligand-based pharmacophore methodology, was performed to indicate the most suitable contact sites in compounds towards 1z8l & 3rcd proteins. The search hits several compounds reach 3,732,214 hits and a closer 3D-fingerprint drug model was obtained. MOE docking was performed for most compounds to explain all interaction features through such simulation process. Best docking scores were recorded with HL-3rcd, Co(II)complex-1z8l, Co(II) complex-3rcd and Cu(II) complex-3rcd by values of −60,628, −6.1447, −6.055 and −6.0626, respectively. Amino acid residues that contributing in allosteric binding were clearly categorized. Finally in-silico approach confirms the superiority of Co(II)-L, Cu(II)-L and free thiophene derivative in controlling human cancer cells, which agree with in vitro results.

Synthesis, characterization, cytotoxicity and computational studies of new phosphine‐ and carbodithioate‐based palladium(II) complexes

In quest of new metallo‐pharmaceuticals with enhanced anticancer activity, four new phosphine‐ and carbodithioate‐based Pd(II) complexes of the type [(R)CS2Pd(PR3)Cl] (where R = 4‐(2‐hydroxyethyl)piperazine (1, 2), dibenzyl (3, 4); PR3 = diphenyl(p‐tolyl)phosphine (1, 3), tris(4‐tolyl)phosphine (2, 4)) were synthesized and characterized using elemental analysis, Fourier transform infrared and NMR (1H, 13C and 31P) spectroscopies and single‐crystal X‐ray diffraction. The X‐ray diffraction data confirmed the pseudo square‐planar geometry ensuring bidentate coordination mode of carbodithioate ligands. Anticancer activity of the synthesized complexes and their ligands was assessed against human lung (A549), breast (MCF‐7) and prostate (PC3) carcinoma cells using MTT assay. All the tested compounds showed activity in micromolar range. In many cases, the cytotoxicity of the synthesized complexes was higher than or comparable to that of the standard drugs cisplatin and doxorubicin. Complex 3 emerged as the most promising compound with the lowest IC50 values of 4.83, 3.72 and 5.11 μM for A549, MCF‐7 and PC3 carcinoma cell lines, respectively. DNA binding studies were also carried out using UV–visible spectroscopy. We extended our investigations to explore the mechanism of anticancer activity using in silico tools. Based on the mechanism of action of standard drugs used, extensive docking studies were carried out on the three different biomolecular targets.