Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC50 values of 39.7 and 28.5 µM, respectively. 7 e and 7 f induced apoptosis and suppressed migration of HCT116 cells. These compounds also induced a significant increase in caspase-3 and CDH1 activities, and a downregulation of Bcl2 using ELISA. pBR322 DNA cleavage activities of cyanoacrylamides were determined using agarose gel electrophoresis. Furthermore, 7 e and 7 f showed good DNA and BSA binding affinities using different spectroscopic techniques. Furthermore, molecular docking for 7 e and 7 f was performed to anticipate their binding capabilities toward various proteins (Bcl2, CDH1 and BSA). The docking results were well correlated with those of experimental results. Additionally, density functional theory and ADMET study were performed to evaluate the molecular and pharmacokinetic features of 7 e and 7 f, respectively. Thus, this work reveals promising antitumor lead compounds that merit future research and activity enhancement.

Anticancer behaviour of 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione)-based palladium(II) complex and its DNA, BSA binding propensity and DFT study.

Herein, we report the synthesis and biological evaluation of [Pd(L)(OH2)Cl] complex (where L = 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione) as a novel promising anticancer candidate. The complex was characterized by single-crystal X-ray diffraction and other various spectroscopic techniques. Besides, the optimized structure was determined through DFT calculations revealing that the coordination geometry of [Pd(L)(OH2)Cl] complex is square planar. The binding propensity of [Pd(L)(OH2)Cl] complex with DNA and BSA was assessed by the spectrophotometric method. The antimicrobial profile of the ligand and its [Pd(L)(OH2)Cl] complex was screened against clinically important bacterial strains. [Pd(L)(OH2)Cl] complex showed promising activity against these microorganisms. Pd(L)(OH2)Cl] complex exhibited a potent antiproliferative potential compared to its ligand against different human cancer cells (A549, HCT116, MDA-MB-231, and HepG2) with less toxic effect against normal cells (WI-38). Additionally, [Pd(L)(OH2)Cl] complex exerted its anticancer effects against the most responsive cells (HCT116 cells; IC50 = 11 ± 1 µM) through suppressing their colony-forming capabilities and triggering apoptosis and cell cycle arrest at S phase. Quantitative PCR analysis revealed a remarkable upregulation of the mRNA expression level of p53 and caspase-3 by 4.8- and 5.9-fold, respectively, relative to control. Remarkable binding properties and non-covalent interactions between L and its [Pd(L)(OH2)Cl] complex with the binding sites of different receptors including CDK2, MurE ligase, DNA, and BSA were established using molecular docking. Based on our results, [Pd(L)(OH2)Cl] complex is an intriguing candidate for future investigations as a potential anticancer drug for the treatment of colon cancer.

Synthesis of a new sulfadimidine Schiff base and their nano complexes as potential anti-COVID-19 and anti-cancer activity.

The primary objective of this study was to describe the cytotoxicity on HEPG-2 cells and to study the COVID­19 activities of the novel H2L ligand and its Cr and Cu nano-complexes. As well as exploring the chemistry of the prepared nano-complexes. In this paper novel Schiff base, N-(4, 6-dimethyl pyrimidin-2-yl)-4-(((2-hydroxyl naphthalene-1-y l) methylene) amino) benzene-sulfonamidesulfonyl) amide has been synthesized. The novel Schiff base H2L is used to synthesize novel nano and micro-complexes with CrCl2.6H2O and CuCl2.2H2O. The prepared ligand and micro complexes were interpreted by different spectroscopic techniques. The nano-sized Cr and Cu complexes were synthesized in an environmentally friendly manner using Coriandrum sativum (CS) media extract in ethanol. The structure, morphologies and particle size of the nano-sized complexes were determined using FT-IR, TEM, and PXRD. The results showed that the nano-domain complexes are on the Sub-nano scale. Furthermore, using TGA, we studied the effect of heat on the size of newly prepared nano-complexes. Experimental data were supported by DFT calculations. The findings revealed that the metal complexes investigated are more stable than the free ligand H2L. The antitumor activity was examined before and after heating the nano-complexes at 200 °C. The results reveal the Cr nano complex, after heating, exhibited strong antitumor activity with IC50 value (3.349 µg/ml). The tested Cu nano-complex shows good DNA cleavage. The liver cancer and COVID19 proteins were examined using molecular docking to identify the potential binding energy of inhibitors.

Oxidative DNA cleavage mediated by a new unexpected [Pd(BAPP)][PdCl4] complex (BAPP = 1,4-bis(3-aminopropyl)piperazine): crystal structure, DNA binding and cytotoxic behavior.

A novel Pd(ii) double complex, [Pd(BAPP)][PdCl4], containing the 1,4-bis(3-aminopropyl)piperazine (BAPP) ligand is investigated. X-ray crystallography of a single crystal confirmed the structure of the [Pd(BAPP)][PdCl4] complex. The spectroscopic behavior was also elucidated using elemental analysis, nuclear magnetic resonance and Fourier-transform infrared spectroscopy, and mass spectrometry. The antimicrobial susceptibility of the [Pd(BAPP)][PdCl4] complex against all tested microbial strains was lower than that of the BAPP ligand except for C. albicans. The cytotoxic impacts of the BAPP ligand and its [Pd(BAPP)][PdCl4] complex were evaluated in vitro for HepG2, CaCo-2 and MCF7 cell lines as well as the WI-38 normal cell line. The anticancer activity was markedly improved by the complexation. The [Pd(BAPP)][PdCl4] complex could selectively inhibit the tested cancer cells in a safe way to the non-tumorigenic cell (WI-38). From the DNA binding studies with ultraviolet-visible spectrophotometry, the [Pd(BAPP)][PdCl4] complex interacts more efficiently with the calf thymus DNA than its BAPP ligand through the intercalative binding mode. In the absence of an external reductant, the [Pd(BAPP)][PdCl4] complex cleaved the intact supercoiled pBR322 DNA under physiological conditions in a concentration-dependent manner. Additionally, electrophoretic experiments were performed in the presence of different radical scavengers, namely DMSO, NaN3 and KI, and ruled out the hydrolytic mechanistic pathway of the reaction and suggested that the oxidative mechanism is the preferred one. The results of the binding affinity of the [Pd(BAPP)][PdCl4] complex to human DNA were modeled using a molecular docking study showing that the complex interacts more strongly with human DNA than the ligand. Finally, an in vitro pharmacokinetic study was assessed through in silico ADME predictions.

DNA/lysozyme binding propensity and nuclease properties of benzimidazole/2,2'-bipyridine based binuclear ternary transition metal complexes.

In the present contribution, new binuclear ternary complexes; [M2(bpy)4L](ClO4)4 (M = Co(ii) (1) and Ni(ii) (2); bpy = 2,2'-bipyridine; L = 1,1'-(hexane-1,6-diyl)bis[2-(pyridin-2-yl)1H-benzimidazole] and [Cu2(bpy)2(OH2)2L](BF4)4 (3) were synthesized, characterized and screened for their antimicrobial activity and cytotoxicity against human liver carcinoma cells (HepG-2) as well as non-malignant human embryonic kidney cells (HEK-293). The structural studies were complemented by density functional theory (DFT) calculations. DNA binding of 1-3 was spectrophotometrically studied. The DNA cleavage ability of 1-3 towards the supercoiled plasmid DNA (pBR322 DNA) was examined through gel electrophoresis. Compound 3 has the highest cytotoxic activity (IC50 = 3.5 µg mL-1) against HepG-2 among the investigated complexes and is non cytotoxic to noncancerous HEK-293. Complexes (1 and 2) exhibited toxicity to HEK-293 with IC50 values of 30.3 and 23.5 µg mL-1 in that order. While compound 1 showed antifungal activity against Cryptococcus neoformans, complex 2 exhibited its toxicity against Candida albicans.

Synthesis and structural characterization of Pd(N,N-dimethylaminopropylamine)Cl2 complex--the interaction with bio-relevant ligands with reference to the effect of cysteine on the deactivation of metal-based drug.

The synthesis and X-ray structural characterization of Pd(DMPA)Cl(2) complex, where DMPA=N,N-dimethylaminopropylamine, is reported. The complex crystallizes in the space group P2(1)/c, a=8.8923(4), b=10.9050(5), c=11.5006(7) Å, ß=120.00(18)°, V=948.25(8) Å(3), Z=4. The palladium centre has a typical square-planar geometry with a tetrahedral distortion. Stoichiometry and stability constants of the complexes formed between [Pd(DMPA)(H(2)O)(2)](2+) and some selected DNA constituents and cytsteine are investigated at 25 °C and at constant 0.1M ionic strength. The concentration distribution diagrams of the various species formed are evaluated. The equilibrium constants for the displacement of coordinated ligands as inosine by cysteine are calculated. The results are expected to contribute to the chemistry of tumour therapy.