A combined study of quantum chemical calculation and molecular docking of some hydantoin and thiohydantoin related compounds

The various classes of hydantoin and thiohydantoin compounds, many of which have extensive biological activities, have been intensively investigated in recent years. The quantum chemical properties and the molecular docking of a set of seven hydantoin and thiohydantoin related heterocyclic compounds containing cyclic urea and thiourea nuclei have been studied here. Dipole moment, frontier orbital gap, absolute hardness, and total energy of these compounds have been investigated. These compounds have been subsequently docked against the ligand-binding domain of the human androgen receptor (hAR). Molecular docking against the human androgen receptor demonstrate the variation in ligand binding affinity and show that TRP751, ARG752, GLU681, ASN756, and ALA748 amino acids play a critical role in ligand binding. According to molecular docking studies, L2 exhibits the best binding affinity of −8.3 kcal/mol with AR. Therefore, our studies suggest that the compound (L2) may be a promising candidate for further evaluation for PCa prevention or management

A combined study of quantum chemical calculation and molecular docking of some hydantoin and thiohydantoin related compounds

1103-1112The various classes of hydantoin and thiohydantoin compounds, many of which have extensive biological activities, have been intensively investigated in recent years. The quantum chemical properties and the molecular docking of a set of seven hydantoin and thiohydantoin related heterocyclic compounds containing cyclic urea and thiourea nuclei have been studied here. Dipole moment, frontier orbital gap, absolute hardness, and total energy of these compounds have been investigated. These compounds have been subsequently docked against the ligand-binding domain of the human androgen receptor (hAR). Molecular docking against the human androgen receptor demonstrates the variation in ligand binding affinity and show that TRP751, ARG752, GLU681, ASN756, and ALA748 amino acids play a critical role in ligand binding. According to molecular docking studies, L2 exhibits the best binding affinity of -8.3 kcal/mol with AR. Therefore, our studies suggest that the compound (L2) may be a promising candidate for further evaluation for PCa prevention or management

Cytotoxicity, 2D-and 3D-QSAR Study of some Halogen Containing Hydroxy and Amino Substituted Aromatic Compounds

Abstract A set of 24 halogen containing hydroxy and amino substituted aromatic compounds were subjected to 2D-and 3D-QSAR studies. 3D-QSAR was studied at a 2.0 Ǻ 3D grid spacing using molecular interaction fields (MIFs) analysis. The best predictive models by MIFs gave the cross-validated correlation coefficient, Q 2 of 0.668 and squared correlation coefficient, R 2 of 0.979 and the models by MLR, PCR and PLSR methods for 2D-QSAR provided a highly significant squared correlation coefficient (

A novel chromonyl thiohydantoin with anti-proliferative action on primary hepatocellular carcinoma cells

Chromone, imidazolidinedione, thiohydantoin and 2,4-thiazolidinedione structures are known to be cytotoxic to cancer cells. In this study, biological activities of previously synthesized 18 chromonyl-2,4-thiazolidinediones/imidazolidinediones/thiohydantoins were tested by sulforhodamine B assay in five liver and one breast cancer cell lines. It was shown that a hybrid chromonyl thiohydantoin derivative C9 was able to significantly suppress the proliferation of the liver cancer cell lines which are very resistant to anticancer drugs. According to 50% growth inhibition concentrations of C9, well differentiated hepatocellular carcinoma cell line Huh7 and breast adenocarcinoma cell line Mcf7 cells are found to be highly sensitive to C9 with IC50 values between 4.9-5.2 mu M. Poorly differentiated human liver cancer cell line Snu449 is found to be the most resistant to C9. Further studies show that C9 causes morphological changes in Snu449 cells. However, it does not induce significant senescence response or cell cycle arrest. On the other hand, Huh7 cells are found to be arrested in G2/M phase of the cell cycle after 24 and 72 h treatment. In conclusion, a novel chromonyl thiohydantoin hybrid molecule effectively stops or slows down the proliferation of well-differentiated hepatocellular carcinoma cells that exist in primary tumors

Rationalization of the p<i>K</i>_a values of alcohols and thiols using atomic charge descriptors and its application to the prediction of amino acid p<i>K</i>_a's

In a first step toward the development of an efficient and accurate protocol to estimate amino acids' pK(a)'s in proteins, we present in this work how to reproduce the pK(a)'s of alcohol and thiol based residues (namely tyrosine, serine, and cysteine) in aqueous solution from the knowledge of the experimental pK(a)'s of phenols, alcohols, and thiols. Our protocol is based on the linear relationship between computed atomic charges of the anionic form of the molecules (being either phenolates, alkoxides, or thiolates) and their respective experimental pK(a) values. It is tested with different environment approaches (gas phase or continuum solvent-based approaches), with five distinct atomic charge models (Mulliken, Lowdin, NPA, Merz-Kollman, and CHelpG), and with nine different DFT functionals combined with 16 different basis sets. Moreover, the capability of semiempirical methods (AM1, RM1, PM3, and PM6) to also predict pK(a)'s of thiols, phenols, and alcohols is analyzed. From our benchmarks, the best combination to reproduce experimental pK(a)'s is to compute NPA atomic charge using the CPCM model at the B3LYP/3-21G and M062X/6-311G levels for alcohols (R-2 = 0.995) and thiols (R-2 = 0.986), respectively. The applicability of the suggested protocol is tested with tyrosine and cysteine amino acids, and precise pK(a) predictions are obtained. The stability of the amino acid pK(a)'s with respect to geometrical changes is also tested by MM-MD and DFT-MD calculations. Considering its strong accuracy and its high computational efficiency, these pK(a) prediction calculations using atomic charges indicate a promising method for predicting amino acids' pK(a) in a protein environment