Integrating experimental and computational approaches to explore the anticancer potential of a pyridine-based reduced Schiff base.

Synthesis and anticancer activity of Pd(II) and Pt(II) complexes of dodecyl based dithiocarbamate ligands: Insight into the C-H∙∙∙Pt interaction using X-ray structure, DFT, Hirshfeld surface and AIM analysis

Phytochemical constituents have been participated with essential role in the discovery of several clinically effective anticancer agents. The goal of this study was to isolate phytoconstituents from Koelreuteria elegans twigs (Sapindacea family) and evaluate their anticancer activities against human lung, colon and breast carcinoma cell lines. The aqueous methanol extract of plant's twigs was fractionated with different solvents and the preliminary cytotoxicity of fractions was determined using brine shrimp lethality assay. Nine compounds from K. elegans twigs butanol fraction were isolated for the first time; gallic acid (1), methyl gallate (2), 6-O- [Galloyl 4- methyl ether]-(α/β)-D-glucopyranose (3), 3, 5-di-O-galloylquinic acid butyl ester (4), 3,4,5-tri-O-galloylquinic acid butyl ester (5), 1,3,4,5-tetra-O-galloylquinic acid butyl ester (6), two isomers of 3-O-galloyl quinic acid butyl ester and 4-O-galloyl quinic acid butyl ester (7), austrobailignan 1 (8) and β-sitosterol (9). The structures of compounds were elucidated using different spectroscopic techniques. Anticancer activities of butanol fraction, methyl gallate and austrobailignan 1were estimated in-vitro by cell viability assay. The results showed significant anticancer activity of both methyl gallate and austrobailignan 1 against breast carcinoma cell lines and less cytotoxicity against colon carcinoma cell lines while almost no activity against lung carcinoma cell lines.

2,6-disubstituted imidazothiadiazole 5-carbaldehyde: Synthesis, crystal structure elucidation and in-silico studies

Single crystal XRD, Hirshfeld surface analysis and computational approach for exploration of novel xanthene derivative

This study presents the synthesis and thorough characterisation of a hydrazine-hydroxy-pyran-2-one derivative referred to as compound (L1 : 3, 3′- [(1E.2E)-hydrazine-1, 2-diylidene-dieth-1-yl-1-ylidene] bis(4-hydroxy-6-methyl-2H-pyran-2-one). Structural elucidation using UV-vis, FT-IR and single crystal X-ray diffraction (SC-XRD) confirmed tautomeric forms of L1 . The SC-XRD analysis revealed a bi-zwitterionic form (BZL1 ), stabilised by the intramolecular proton transfer between two enol units and azine tautomerism. The planar molecular structure, supported by XRD, DFT and Hirshfeld surface analysis, showed charge-assisted hydrogen bonds [N+−H…O−] forming S(6) ring motifs. Crystals were stabilised by C-H…O hydrogen bonds and π-π stacking, analysed through Hirshfeld surfaces and 2D fingerprint plots. Compound L2 : 3-[(1E)-1-(9H-fluoren-9-ylidenehydrazinylidene)ethyl]-4-hydroxy-6-methyl-2H-pyran-2-one), is illustrated in this paper to compare two derivatives of dehydroacetic acid (DHA) and to enrich this study. Molecular docking revealed binding affinities of hybrid compounds with target proteins. DFT and TD-DFT analyses examined structural, electronic and optical properties, aligning well with experimental data. BZL1 exhibited higher electronic hardness (3.632 eV) than L2 (3.506 eV). Variations in α, Δα and ρ values were observed, with L1 showing stronger γ(0; 0, 0, 0) and γ(−ω; ω, 0, 0) while L2 excelled in γ(−2ω; ω, ω, 0). Consequently, these results highlight the potential of these compounds as promising candidates for use in third-order nonlinear optical applications.

Structural and optical properties of salicyl-N-methyl-4-stilbazolium tosylate: Thermal, DFT, MEP and Hirshfeld surface analysis

Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines

Synthesis, Single Crystal XRD, In-Silico and In-Vitro Studies of Alkyl Substituted Acyl Thiourea as Carbonic Anhydrase Inhibitor

Three new hydralazine-based compounds (1–3) were synthesized and characterized by spectroscopic techniques (FT-IR, UV-Vis, NMR, HRMS). The crystal structures of compounds 1 and 2 were determined by single-crystal XRD. The compounds exhibit diverse tautomeric forms and distinct supramolecular organizations governed by hydrogen bonding and π–π stacking interactions. Structural studies in both compounds 1 and 2 revealed that both phthalazine and phenyl rings are nearly coplanar, promoting extended conjugation and rigidity. Hirshfeld surface and energy framework analyses indicate that H···H, N···H, O···H, and Cl···H contacts are the dominant contributors to crystal packing stability. DFT calculations generated optimized geometries and electronic parameters consistent with experimental results. Frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) analyses revealed that compound 1 possesses the highest HOMO energy and dipole moment, indicating its higher donor ability and polar character. These combined experimental and theoretical investigations offer valuable insights into the structure–property relationships of hydralazine-derived compounds.

Synthesis, biological evaluation and X-ray crystallographic analysis of novel (E)-2-cyano-3-(het)arylacrylamides as potential anticancer agents

The [Ag(3ADMT)(NO3)]n complex was synthesized by the self-assembly of 3-amino-5,6-dimethyl-1,2,4-triazine (3ADMT) and AgNO3. Its molecular structure was analyzed utilizing FTIR spectra, elemental analysis, and single crystal X-ray diffraction (SC-XRD). There is one crystallographically independent Ag atom, which is tetra-coordinated by two nitrogen atoms from two 3ADMT and two oxygen atoms from two nitrate anions where all ligand groups are acting as connectors between the Ag1 sites. The geometry around the Ag(I) center is a distorted tetrahedron with a AgN2O2 coordination sphere augmented by strong argentophilic interactions between Ag atoms, which assist the aggregation of the complex units in a wavy-like and coplanar pattern to form a one-dimensional polymeric chain. The O...H (37.2%) and N...H (18.8%) intermolecular interactions contributed significantly to the molecular packing based on Hirshfeld surface analysis. The [Ag(3ADMT)(NO3)]n complex demonstrates promising cytotoxicity against lung (IC50 = 2.96 ± 0.31 μg/mL) and breast (IC50 = 1.97 ± 0.18 μg/mL) carcinoma. This remarkable cytotoxicity exceeds those of 3ADMT, AgNO3, and the anticancer medication cis-platin towards the tested cancer cell lines. In addition, the complex has a wide-spectrum antimicrobial action where the high antibacterial potency of the [Ag(3ADMT)(NO3)]n complex against P. vulgaris (MIC = 6.1 µg/mL) and B. subtilis (MIC = 17.2 µg/mL) could be comparable to the commonly used drug Gentamycin (MIC = 4.8 µg/mL). These results confirm that the components of the [Ag(3ADMT)(NO3)]n complex work together synergistically, forming a powerful multifunctional agent that could be exploited as an effective antimicrobial and anticancer agent.

Synthesis, spectral characterization and X-ray crystal structure studies of 3-(benzo[d][1,3]dioxol-5-yl)-5-(3-methylthiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-carboxamide: Hirshfeld surface, DFT and thermal analysis

A rhodanine derivative as a potential antibacterial and anticancer agent: Crystal structure, spectral characterization, DFT calculations, Hirshfeld surface analysis, in silico molecular docking and ADMET studies

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

Brevifoliol is a diterpenoid that occurs naturally in the plants of Taxus genus and is widely used as chemotherapy agent for the management of cancer. A series of semisynthetic esters analogues of brevifoliol were prepared by Steglich esterification and attempted for their pharmacological potential against insulin resistance conditions using in-vitro and in-silico assays. The aim of this study is to understand the pharmacological potential of eighteen semisynthetic analogs through Steglich esterification of Brevifoliol against insulin resistance condition. In the in-vitro study, insulin resistance condition was induced in skeletal muscle cells using TNF-α, pro-inflammatory cytokine and these cells were treated with brevifoliol analogues. The most potent analouge was further validated using in-silico docking study against the tumor necrosis factor (TNF-α) (PDB ID: 2AZ5) and Human Insulin Receptor (PDB ID: 1IR3), using the Auto dock Vina v0.8 program. Although, all the analogues of Brevifoliol significantly exhibited the pharmacological potential. Among all, analogue 17 was most potent in reversing the TNF-α induced insulin resistance condition in skeletal muscle cells and also to inhibit the production of TNF-α in LPSinduced inflammation in macrophage cells in a dose-dependent manner. Similarly, in-silico molecular docking studies revealed that analogue 17 possesses a more promising binding affinity than the selected control drug metformin toward the TNF-α and insulin receptor. These findings suggested the suitability of analogue 17 as a drug-like candidate for further investigation toward the management of insulin resistance conditions.