Data-Driven Modelling of Substituted Pyrimidine and Uracil-Based Derivatives Validated with Newly Synthesized and Antiproliferative Evaluated Compounds.

The pyrimidine heterocycle plays an important role in anticancer research. In particular, the pyrimidine derivative families of uracil show promise as structural scaffolds relevant to cervical cancer. This group of chemicals lacks data-driven machine learning quantitative structure-activity relationships (QSARs) that allow for generalization and predictive capabilities in the search for new active compounds.

Structure of Biologically Active Benzoxazoles: Crystallography and DFT Studies.

Using X-ray single crystal diffraction, the crystal structures of biologically active benzoxazole derivatives were determined. DFT calculation was performed with standard 6-31G*(d), 6-31G** and 6-31+G* basis set to analyze the molecular geometry and compare with experimentally obtained X-ray crystal data of compounds. The calculated HOMO-LUMO energy gap in compound 2 (2-(2-hydroxynaphtalen-1-yl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol) is 3.

Quantitative structure-activity relationships of xanthen-3-one and xanthen-1,8-dione derivatives and design of new compounds with enhanced antiproliferative activity on HeLa cervical cancer cells.

Xanthene derivatives have become a group of molecules of great importance in discovering of new anticancer drugs. Recent studies of our group performed on xanthen-3-one and xanthen-1,8-dione derivatives have shown their antiproliferative activity on HeLa cervical cell lines. Obtained IC values together with calculated molecular descriptors were subjected to Quantitative Structure-Activity Relationship (QSAR) study in order to identify the most relevant molecular features responsible for the observed antiproliferative activity of compounds.

Antiproliferative and genotoxic potential of xanthen-3-one derivatives.

Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4' position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.

Synthesis, Biological Evaluation and Docking Studies of Benzoxazoles Derived from Thymoquinone.

Thymoquinone (), a natural compound with antimicrobial and antitumor activity, was used as the starting molecule for the preparation of 3-aminothymoquinone () from which ten novel benzoxazole derivatives were prepared and characterized by elemental analysis, IR spectroscopy, mass spectrometry and NMR (¹H, C) spectroscopy in solution. The crystal structure of 4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazole-5-ol () has been determined by X-ray diffraction. All compounds were tested for their antibacterial, antifungal and antitumor activities.

9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one is a Potentially Novel Antiplatelet Drug which Antagonizes the Effect of Thromboxane A2.

Background: Currently, used oral antiplatelet drugs are both limited and associated with the risk of treatment failure/resistance. Research in this area is hence highly desired. A series of xanthene-3-ones derivatives, we had synthesized, showed us that these derivatives had antiplatelet activity.

Cytogenotoxicity of Inclusion Complexes of Diazepam with 2-Hydroxypropyl-β-cyclodextrin.

Diazepam, as one of the most frequent prescribed drug from 1,4-benzodiazepine group, has certain limitations in pharmaceutical technology due to its poor solubility in water. By forming inclusion complexes with 2-hydroxypropyl-β-cyclodextrin, diazepam's biopharmaceutical properties can be greatly improved. Aim of this research was to in vitro evaluate genotoxicity of prepared novel complexes of diazepam and their influence on proliferation of human peripheral blood lymphocytes.

C-5 hydroxyethyl and hydroxypropyl acyclonucleosides as substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK): syntheses and biological evaluation.

The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK.

Benzylidene-bis-(4-hydroxycoumarin) and benzopyrano-coumarin derivatives: synthesis, ¹H/¹³C-NMR conformational and X-ray crystal structure studies and in vitro antiviral activity evaluations.

We report on the synthesis of 4-hydroxycoumarin dimers 1-15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16-20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The chemical identities and structure of compounds 1-20 were deduced from their homo- and heteronuclear NMR measurements whereas the conformational properties of 5, 14 and 20 were assessed by the use of 1D difference NOE enhancements. Unequivocal proof of the stereostructure of compounds 7, 9, 16 and 18 was obtained by single crystal X-ray diffraction method.

The synthesis and antimicrobial activity of some 4-hydroxycoumarin derivatives.

Due to exceptional reactivity of 4-hydroxycoumarin, the synthesis of new coumarin derivatives of dimer and tetramer type has been carried out. The synthesis was carried out from 4-hydroxycoumarin and various aromatic aldehydes. In this way, compounds of the dimer 3,3'-(benzilidene)bis (4-hydroxycoumarin) type, as well as of the tetramer 3,3',3'',3'''-(1,4-dimethylenphenyl)tetra (4-hydroxycoumarin) type were prepared.

[Antidepressives and antidepressive interactions with other drugs].

During the therapy with antidepressive agents, for the reason of its duration, numerous drug-drug interactions may occur. Antidepressive agents inhibit P450 enzyme activity and interfere with other drug metabolism. Many interactions are acceptable from the clinical point of view, and some are seriously dangerous indicating a need for their better knowledge.

QSAR and QSPR study of derivatives 4-arylaminocoumarin.

Coumarin and its derivatives are reactive compounds, suitable for many syntheses. They are used as anticoagulants, antibacterial, animistic compounds. The interest in coumarins has increased because it was found that they reduce the HIV virus activity.

The 4-arylaminocoumarin derivatives log P values calculated according to Rekker's method.

In the QSAR (quantitative structure-activity relationship) and QSPR (quantitative structure-property-activity relationship) study physico-chemical property, lipophilicity is used, to predict bioactivity of the newly synthesized coumarin compounds. Lipophilicity is a property of a molecule which depends on and can be changed by modifications in molecular structure. The parameter of the lipophilicity, partition coefficient (log P), is commonly used in drug designing and it is a numeric characteristic of lipophilicity of the examined substance, potential drug.