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Recently, 5-[(4-ethoxyphenyl)imino]methyl-N-(4-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine has been synthesized, characterized, and evaluated for its antibacterial activity against Enterococcus faecalis in combination with antineoplastic activity against gastric adenocarcinoma. In this study, new 5-iminomethylpyrimidine compounds were synthesized which differ in the substituent(s) of the aromatic ring attached to the imine group. The structures of newly obtained pyrimidine Schiff bases were established by spectroscopy techniques (ESI-MS, FTIR and 1H NMR). To extend the current knowledge about the features responsible for the biological activity of the new 5-iminomethylpyrimidine derivatives, low-temperature single-crystal X-ray analyses were carried out. For all studied crystals, intramolecular N–H∙∙∙N hydrogen bonds and intermolecular C–H∙∙∙F interactions were observed and seemed to play an essential role in the formation of the structures. Simultaneously, their biological properties based on their cytotoxic features were compared with the activities of the Schiff base (III) published previously. Moreover, computational investigations, such as ADME prediction analysis and molecular docking, were also performed on the most active new Schiff base (compound 4b). These results were compared with the highest active compound III.

Thiazolo[4,5-d]pyrimidine derivatives are considered potential therapeutic agents, particularly in the development of anticancer drugs. In this study, new 7-oxo-(2a-e), 7-chloro-(3a-e) and also three 7-amino-(4a-c) 5-trifluoromethyl-2-thioxo-thiazolo[4,5-d]pyrimidine derivatives have been synthesized and evaluated for their potential anticancer activity. These derivatives were characterized by spectroscopic methods and elemental analysis, and the single-crystal X-ray diffraction was further performed to confirm a 3D structure for compounds 2e and 4b. The antiproliferative activity evaluation of twelve new compounds was carried out on a variety of cell lines including four human cancer (A375, C32, DU145, MCF-7/WT) and two normal cell lines (CHO-K1 and HaCaT). Four of them (2b, 3b, 4b and 4c) were selected by the National Cancer Institute and evaluated for their in vitro anticancer activity using the NCI-60 screening program. 7-Chloro-3-phenyl-5-(trifluoromethyl)[1,3]thiazolo[4,5-d]pyrimidine-2(3H)-thione (3b) proved to be the most active among the newly synthesized compounds.

Pyrimidine displays a wide array of bioactivities, and thence, it is still considered a potent unit of new drug research. Its derivative, 5-hydroxymethylpyrimidine, can be found as a scaffold of nontypical nitrogen bases in DNA and as a core of some natural bioactive compounds. In this study, we obtained a series of 5-hydroxymethylpyrimidines that vary in the 4-position by the reduction of proper esters. All compounds were characterized by spectroscopic analysis, and single-crystal X-ray diffraction was performed for some of them. Biological investigations estimated cytotoxic properties against normal (RPTEC) and cancer (HeLa, HepaRG, Caco-2, AGS, A172) cell lines. It was found that the derivatives with an aliphatic amino group at the 4-position are generally less toxic to normal cells than those with a benzylsulfanyl group. Moreover, compounds with bulky constituents exhibit better anticancer properties, though at a moderate level. The specific compounds were chosen due to their most promising IC50 concentration for in silico study. Furthermore, antimicrobial activity tests were performed against six strains of bacteria and one fungus. They demonstrated that only derivatives with at least three carbon chain amino groups at the 4-position have weak antibacterial properties, and only the derivative with 4-benzylsulfanyl constituent exhibits any antifungal action.

Enterococcus faecalis is known as a significant nosocomial pathogen due to its natural resistance to many antibacterial drugs. Moreover, it was found that E. faecalis infection causes inflammation, production of reactive oxygen species, and DNA damage to human gastric cancer cells, which can induce cancer. In this study, we synthesized and tested the biological activity of a new Schiff base, 5-[(4-ethoxyphenyl)imino]methyl-N-(4-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine (3), and compared its properties with an analogous amine (2). In the biological investigation, 3 was found to have antibacterial activity against E. faecalis 29212 and far better anticancer properties, especially against gastric adenocarcinoma (human Caucasian gastric adenocarcinoma), than 2. In addition, both derivatives were non-toxic to normal cells. It is worth mentioning that 3 could potentially inhibit cancer cell growth by inducing cell apoptosis. The results suggest that the presence of the –C=N– bond in the molecule of 3 increases its activity, indicating that 5-iminomethylpyrimidine could be a potent core for further drug discovery research.

The synthesis of a series of novel 7-aminooxazolo[5,4-d]pyrimidines 5, transformations during their synthesis and their physicochemical characteristics have been described. Complete detailed spectral analysis of the intermediates 2–4, the N′-cyanooxazolylacetamidine by-products 7 and final compounds 5 has been carried out using MS, IR, 1D and 2D NMR spectroscopy. Theoretical research was carried out to explain the privileged formation of 7-aminooxazolo[5,4-d]pyrimidines in relation to the possibility of their isomer formation and the related thermodynamic aspects. Additionally, the single-crystal X-ray diffraction analysis for 5h was reported. Ten 7-aminooxazolo[5,4-d]pyrimidines 5 (SCM1–10) were biologically tested in vitro to preliminarily evaluate their immunological, antiviral and anticancer activity. Compounds SCM5 and SCM9 showed the best immunoregulatory profile. The compounds displayed low-toxicity and strongly inhibited phytohemagglutinin A-induced proliferation of human peripheral blood lymphocytes and lipopolysaccharide-induced proliferation of mouse splenocytes. Compound SCM9 caused also a moderate suppression of tumor necrosis factor α (TNF-α) production in a human whole blood culture. Of note, the compounds also inhibited the growth of selected tumor cell lines and inhibited replication of human herpes virus type-1 (HHV-1) virus in A-549 cell line. Molecular investigations showed that the compounds exerted differential changes in expression of signaling proteins in Jurkat and WEHI-231 cell lines. The activity of SCM5 is likely associated with elicitation of cell signaling pathways leading to cell apoptosis. The compounds may be of interest in terms of therapeutic utility as inhibitors of autoimmune disorders, virus replication and antitumor agents.

Thanks to the progress in oncology, pharmacological treatment of cancer is gaining in importance and in the near future anti-cancer chemotherapeutics are expected to be the main method of treatment for cancer diseases. What is more, the search for new anti-cancer compounds with the desired application properties is constantly underway. As a result of designed syntheses, we obtained some new N’-substituted 5-chloro-3-methylisothiazole-4-carboxylic acid hydrazide derivatives with anticancer activity. The structure of new compounds was determined by mass spectrometry (MS), elemental analysis, proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), 1H-13C NMR correlations and infrared spectroscopy (IR). Moreover, the structures of the compounds were confirmed by crystallographic examination. The antiproliferative MTT tests for 11 prepared compounds was conducted towards human biphenotypic B cell myelomonocytic leukemia MV4-11. SRB test was used to examine their potential anticancer activity towards human colon adenocarcinoma cell lines sensitive LoVo, resistant to doxorubicin LoVo/DX, breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A. The most active compound was 5-chloro-3-methyl-N′-[(1E,2E)-(3-phenyloprop-2-en-1-ylidene]isothiazole-4-carbohydrazide, which showed the highest antiproliferative activity against all tested cell lines.