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[Display omitted] • Cyclin-dependent kinases (CDKs) are a family of protein-serine kinases. • Heterocyclic rings have demonstrated encouraging efficacy in inhibiting cyclin-dependent kinase activity. • CDK kinase inhibitors for the treatment of cancer. • Molecular interactions with receptor. Cyclin-dependent kinases (CDKs) constitute a vital family of protein-serine kinases, pivotal in regulating various cellular processes such as the cell cycle, metabolism, proteolysis, and neural functions. Dysregulation or overexpression of CDK kinases is directly linked to the development of cancer. However, the currently approved CDK inhibitors by the US FDA, such as palbociclib, ribociclib, Trilaciclib, Abemaciclib, etc., although effective, exhibit limited specificity and often lead to undesirable adverse effects. First and second-generation CDK inhibitors have not gained significant clinical interaction due to their high toxicity and lack of specificity. To address these challenges, a combined approach is being employed in the quest for newer CDK inhibitors aimed at mitigating toxicity and side effects associated with CDKIs. The discovery of therapeutic agents selectively targeting tumorous cells, such as CDK inhibitors, has demonstrated promise in treating various cancers, including breast cancer. Extensive literature reviews have facilitated the development of novel CDK inhibitors by combining medicinally preferred pyrimidine derivatives with other heterocyclic rings. Pyrimidine derivatives substituted with pyrazole, imidazole, benzamide, benzene sulfonamide, indole carbohydrazide, and other privileged heterocyclic rings have shown encouraging efficacy in inhibiting cyclin-dependent kinase activity. This review provides comprehensive data, including structure–activity relationship (SAR), anticancer activity, and kinetics studies of potent compounds. Additionally, molecular docking studies with compounds under clinical trial and patents filed on pyrimidine based CDK inhibitors in cancer treatment are included. This review serves as a valuable resource for further development of CDK kinase inhibitors for cancer treatment, offering insights into their efficacy, specificity, and potential clinical applications. [ABSTRACT FROM AUTHOR]

Synthesis and crystal structure with extensive biological activity of the copper sulfadimethoxine complex in the presence of secondary ligand 3-methyl pyridine (title molecule) has been reported earlier. Crystal structure of the title molecule crystallizes in monoclinic space group P21/n. The extension of this work, stability, and reactivity of the title molecule are carried out in the DFT platform using Schrödinger software at B3LYP/LAV2P** level. The theoretically optimized structure of the title molecule in gaseous phase is well matched with the X-ray data. The chemical nature of molecule can be analyzed by employing quantum chemical calculations and HOMO-LUMO energies of the title molecule show the charge transfer occurs within the molecule. The individual atomic charge values are obtained from the Mulliken population analysis (MPA), which reveal the binding site of the title molecule. The stability of the title molecule arising from hyper-conjugative interactions and charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The effect of nitrogen and oxygen atoms on weak intermolecular interactions has been systematically analyzed via energy framework analysis for title molecule. The molecular docking study has been confirmed the title molecule interacts with DNA in a groove binding site. [ABSTRACT FROM AUTHOR]

Quantum descriptors of cadmium complex of sulfamethazine and free ligand sulfamethazine are calculated, and the result of these studies has revealed that complex molecule is having high negative dock energy as compared to that of free ligand. Molecular docking studies have been performed against enzyme receptor to rationalize the inhibitory properties of cadmium complex and free ligand. Results demonstrated that metal complexes are stronger inhibitors of protein molecules as compared to free ligand, which warrant further development of organo-metallics as active inhibitors. The author has synthesized and worked out the 3D structure independently to carry out density functional theory studies and Hirshfeld surface analysis of the complex. Cadmium complex of sulfamethazine has been synthesized and characterized by IR and 1H NMR spectroscopy. Antimicrobial activity has been studied with gram-positive and gram-negative bacteria to understand the biological activity of the title molecule and compared with free ligand. [ABSTRACT FROM AUTHOR]

The synthesis of the compound and its crystal structure having a monoclinic crystal system has been reported earlier. Optimized bond lengths and angles are showing good agreements with experimental data using DFT/B3LYP method. Energy of highest occupied molecular orbital and lowest unoccupied molecular orbital has been predicted to analyze the stabilities of compound. Crystal explorer 17.5 helps to visualize intermolecular interactions and its contributions to each interaction within molecule. The preeminence of dispersion energy component over the other components was established by interaction energy calculations and lattice energy framework analysis using same software. The molecular docking study was performed for molecule using AutoDock software. [ABSTRACT FROM AUTHOR]

Abstract The synthesis, optical characterization and crystal structure with biological activity of novel (Z)-2-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-3,4-dihydronaphthalen 1-(2H)-one (Z2H) has been reported. Crystal structure reports with monoclinic system and space group is P21/c. The extension of this work, stability and reactivity are explored using DFT platform with B3LYP[6-11G(d,p)] basic set. Mulliken charge and HOMO–LUMO energy result indicate that the charge transfer within the molecule. The strong and weak intermolecular interactions of Z2H have been systematically analyzed using Hirshfeld surface analysis. Interaction energy are carried out and indicate that the dispersion energy framework is dominated over the electrostatic energy-frameworks. Lipophilicity index (log P value) represents significant biological activity of the molecules. The molecular docking study confirmed good binding affinity of Z2H with DNA (1BNA), 1h3b and 2p4b. [ABSTRACT FROM AUTHOR]