IMPLEMENTATION OF THE “BIOSYNTHESIS OF NUCLEIC ACIDS AND PROTEINS: GENETIC CODE” TOPIC FOR SECONDARY SCHOOLS FOCUSED ON INFORMATICS

The strategic aim of the “IT Academy – Education for the 21st Century” project was to create an educational model which would prepare young people for the current and future needs of society and the job market, focusing on Informatics and also Information and Communication Technologies. The new subject of Informatics in Natural Sciences and Mathematics consists of five modules that broaden and deepen students\u27 knowledge of Informatics. The Chemistry module focuses on creating models, working with databases, and using selected software programs to teach Chemistry. One of the topics of the module examines the biosynthesis of nucleic acids and proteins, and the use of programming languages such as Python to create genetic code–making models. Students are given the opportunity to work with programming languages, identify differences in the structure and properties of DNA and RNA, and explain the transition of genetic information, transcription and the synthesis of proteins. The content of this task has been selected to present examples of the practical use of Informatics in order to deepen students’ knowledge of Chemistry

Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis, Characterization and ctDNA/HSA Spectroscopic Binding Properties

A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA—ctDNA and human serum albumin—HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents

Novel 3,9-Disubstituted Acridines with Strong Inhibition Activity against Topoisomerase I: Synthesis, Biological Evaluation and Molecular Docking Study

A series of novel 3,9-disubstituted acridines were synthesized and their biological potential was investigated. The synthetic plan consists of eight reaction steps, which produce the final products, derivatives 17a–17j, in a moderate yield. The principles of cheminformatics and computational chemistry were applied in order to study the relationship between the physicochemical properties of the 3,9-disubstituted acridines and their biological activity at a cellular and molecular level. The selected 3,9-disubstituted acridine derivatives were studied in the presence of DNA using spectroscopic (UV-Vis, circular dichroism, and thermal denaturation) and electrophoretic (nuclease activity, relaxation and unwinding assays for topoisomerase I and decatenation assay for topoisomerase IIα) methods. Binding constants (2.81–9.03 × 104 M−1) were calculated for the derivatives from the results of the absorption titration spectra. The derivatives were found to have caused the inhibition of both topoisomerase I and topoisomerase IIα. Molecular docking simulations suggested a different way in which the acridines 17a–17j can interact with topoisomerase I versus topoisomerase IIα. A strong correlation between the lipophilicity of the derivatives and their ability to stabilize the intercalation complex was identified for all of the studied agents. Acridines 17a–17j were also subjected to in vitro screening conducted by the Developmental Therapeutic Program of the National Cancer Institute (NCI) against a panel of 60 cancer cell lines. The strongest biological activity was displayed by aniline acridine 17a (MCF7–GI50 18.6 nM) and N,N-dimethylaniline acridine 17b (SR–GI50 38.0 nM). The relationship between the cytostatic activity of the most active substances (derivatives 17a, 17b, and 17e–17h) and their values of KB, LogP, ΔS°, and δ was also investigated. Due to the fact that a significant correlation was only found in the case of charge density, δ, it is possible to assume that the cytostatic effect might be dependent upon the structural specificity of the acridine derivatives

Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines

A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (hTOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (1c, 1d = tacrine-(CH2)8–9-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains

Chili pepper extracts, capsaicin, and dihydrocapsaicin as potential anticancer agents targeting topoisomerases

Abstract DNA topoisomerases regulate conformational changes in DNA topology during normal cell growth, such as replication, transcription, recombination, and repair, and may be targeted for anticancer drugs. A DNA topology assay was used to investigate DNA-damaging/protective activities of extracts from Habanero Red (HR), Habanero Maya Red (HMR), Trinidad Moruga Scorpion (TMS), Jalapeno (J), Serrano pepper (SP), Habanero Red Savina (HRS), Bhut Jolokia (BJ), and Jamaica Rosso (JR) peppers, demonstrating their inhibitory effect on the relaxation of pBR by Topo I. DNA topoisomerase II (Topo II) is proven therapeutic target of anticancer drugs. Complete inhibition of Topo II was observed for samples TMS, HR, and HMR. Extracts J and SP had the lowest capsaicin and dihydrocapsaicin content compared to other peppers. HR, HMR, TMS, J, S, HRS, BJ, JR extracts showed the anticancer effect, examined by MTS and xCell assay on the in vitro culture of human colon carcinoma cell line HCT116

Synthesis of New Biscoumarin Derivatives, In Vitro Cholinesterase Inhibition, Molecular Modelling and Antiproliferative Effect in A549 Human Lung Carcinoma Cells

A series of novel C4-C7-tethered biscoumarin derivatives (12a–e) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin 12d was found to be the most effective inhibitor of both acetylcholinesterase (AChE, IC50 = 6.30 µM) and butyrylcholinesterase (BChE, IC50 = 49 µM). Detailed molecular modelling studies compared the accommodation of ensaculin (well-established coumarin derivative tested in phase I of clinical trials) and 12d in the human recombinant AChE (hAChE) active site. The ability of novel compounds to cross the blood–brain barrier (BBB) was predicted with a positive outcome for compound 12e. The antiproliferative effects of newly synthesized biscoumarin derivatives were tested in vitro on human lung carcinoma cell line (A549) and normal colon fibroblast cell line (CCD-18Co). The effect of derivatives on cell proliferation was evaluated by MTT assay, quantification of cell numbers and viability, colony-forming assay, analysis of cell cycle distribution and mitotic activity. Intracellular localization of used derivatives in A549 cells was confirmed by confocal microscopy. Derivatives 12d and 12e showed significant antiproliferative activity in A549 cancer cells without a significant effect on normal CCD-18Co cells. The inhibition of hAChE/human recombinant BChE (hBChE), the antiproliferative activity on cancer cells, and the ability to cross the BBB suggest the high potential of biscoumarin derivatives. Beside the treatment of cancer, 12e might be applicable against disorders such as schizophrenia, and 12d could serve future development as therapeutic agents in the prevention and/or treatment of Alzheimer’s disease