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Witaminy z grupy B : opis właściwości fizykochemicznych oraz bioaktywności z wykorzystaniem przykładowych narzędzi cheminformatycznych

Banach Sylwia, Jezierska Aneta

Wiadomości Chemiczne

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2023

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[Z] 77, 9-10

873--896

EN

This paper presents a literature review of the biochemistry of vitamins B and the results of in silico physicochemical properties and bioactivity studies. The description was performed by cheminformatics tools closely related to the field of Medicinal Chemistry. It allows us to predict a great number of properties e.g. logP, TPSA, molecular volume or bioactivity associated with the chosen proteins (like kinases, proteases etc.). These investigations were carried out with the use of cheminformatics web tool Molinspiration. Its great advantages are mainly its wide availability, ease of application and quick analysis of small compounds. Thanks to the comparison with literature data of well–known B vitamins, it is possible to confirm that current cheminformatic web tools provide high reliability of the results and can support Drug Design methods.

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Natural products as potential inhibitors of FLT3 for acute myeloid leukemia: HTVS, docking, and molecular dynamic simulation

Salah Salsabeel, Sami Najat, Ali Sarah, Khalid Teemah-Alrahman, Alnajjar Radwan

Scientiae Radices

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2023

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Vol. 2, Iss. 4

325--346

EN

Cancer is one the most common health issues worldwide, with cancer-related mortality of 9.5 million in 2018, with an expectation to become 29.5 by 2040. Among others, acute myeloid leukemia (AML) is common among older people. FLT3 mutations are one of the most common genetic aberrations found in Acute Myeloid Leukemia and are associated with poor prognosis. Herein, we attempt to identify natural compounds as potential candidates to treat AML by targeting the FLT3 kinase domain using in silico approaches. The COCONUT database, which contains 407,270 natural compounds, was HTVS against the FLT3 kinase domain active site, and promising compounds were subject to molecular docking. Finally, frontier compounds were validated further using molecular dynamic simulation. In total, ten compounds were identified with docking scores higher than Quizartinib (-11.606 kcal/mol), with the best three compounds showing a docking score of -18.052, -15.772, and -16.767 kcal, respectively, and compound 2 showing excellent stability in molecular dynamic simulation.

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Investigation of interactions between dermorphin analogs and µ-opioid receptor

Karczyńska A., Zaborowski B., Ślusarz M.

TASK Quarterly : scientific bulletin of Academic Computer Centre in Gdansk

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2014

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Vol. 18, No 4

331--336

EN

Opioid receptors play the pain control function in the body. Most of the research is carried out to find the most effective analgesic. The earliest analgesic i s morphine, however, unfortunately it has many side effects [Mizoguchi H et al. 2003 J. Pharmacol Sci. 93 423]. At a later time dermorphin was discovered as another potent analgesic [Mont ecucchi P C et al. 1981 Int. J. Pept. Protein Res. 17 275]. Unfortunately, this peptide is not resistant to enzymatic metabolism [Kisara K et al. 1986 Br. J. Pharmacol. 87 183; Sasaki Y et al. 1985 Neuropeptides 5 391]. The objective of this study is to search for new opioid analgesics by in vestigation of interactions between dermorphin analogs and the μ -opioid receptor using molecular modeling methods. MOPR ( μ -Opioid Peptide Receptor) complexes with several ligands (with kno wn biological activity) were modeled to explain how the structure of the complex was related to the biological activity. The investigated dermorphin analogs containing [ DMT 1 , D -Arg 2 ] (especially tetrapeptides) may become a good alternative for the currently used an algesics.

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Docker Analyzer: Program for comparison of docking results

Nielepiec A., Jurkowski W.

Bio-Algorithms and Med-Systems

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2006

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Vol. 2, no. 4

29--36

EN

Vast amount of docking algorithms and scoring functions available encourage development of methods aimed to adjust functionality of docking tools. A certain level of scoring functions precision is needed to recognize complexes of specific intermolecular interactions. Having this kind of model morę detailed blind prediction of molecular complexes would be possible. To enhance specificity of docking results tools unifying application of many scoring functions should be developed. A program for assessment of molecular docking: Docker Analyzer is presented as preliminary approach. Complex calculation of over ten scoring functions and its simultaneous use (multiple consensus scoring) is possible to improve default selection of best hits after standard molecular docking procedure.

PL

Dostępność wielu programów dokujących oraz różnorodność używanych w nich funkcji służących do oceny poprawności kompleksów białko-ligand skłania do ich oceny i porównań. Istotna wydaje się być możliwość dobrania funkcji oceniającej pod kątem specyfiki badanego układu, a więc wybór funkcji, która najpoprawniej w danych przypadku opisywałaby naturę oddziaływań międzycząsteczkowych. Takie podejście powinno pomóc w poprawnym dokowaniu w przypadku kiedy brak jest wstępnej informacji strukturalnej (np. przy nieznanym miejscu wiążącym). Praca ta przedstawia program do oceny efektywności procedur dokowania będący wstępną realizacją takiego podejścia. Program Docker Analyzer umożliwia jednoczesne obliczenie kilkunastu popularnych funkcji oceniających i ich wzajemne porównanie, wyznaczenie na ich podstawie wskaźnika konsensusowego oraz prostą wizualizację kompleksów.

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Lipofilowość, metody wyznaczania i rola w działaniu biologicznym substancji chemicznych

Jóźwiak K., Szumiło H., Soczewiński E.

Wiadomości Chemiczne

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2001

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[Z] 55, 11-12

1047-1074

EN

In this review the current concepts of lipophilicity phenomenon are described. It especially deserves special attention in medicinal chemistry. Lipophilicity is the factor of crucial importance in biological action of chemical substances. It is the main physico-chemical determinant influencing the bioavailability, permeability and frequently the toxicity of drugs. Lipophilicity is thus one of the most important factors in research aimed at rational designing of new drugs, what is of great and still growing importance nowadays. In the present review the current definitions of lipophilicity and hydrophobicity are discussed. Next, the role of lipophilicity of drugs in living organisms is widely reviewed. The experimental methods of estimation of biological lipophilicity are described in their historical development. The most widely used method of measuring the lipophilicity of compounds is nowadays the liquid chromatography technique, especially in reversed phase mode (according to the definition of lipophilicity). RP-HPLC is a fast and very precise tool for determination of lipophilicity in a wide range of chemical compounds. In presented paper the influence of the chromatographic systems are described with special attention on novel stationary phases which closely mimic the biological environment (e.g., Immobilized Artificial Membrane phase). Next, the procedures for the determination of chromatographic lipophilicity parameters for a set of derivatives in polycratic and gradient modes are described. The importance of different retention parameters and their usefulness in assessing lipophilicity are widely examined. Finally, a brief description of calculating methods of lipophilicity estimations is presented.

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Wybrane problemy projektowania substancji biologicznie aktywnych

Polański J.

Wiadomości Chemiczne

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1999

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[Z] 53, 1-2

1-16

EN

Although most of the drugs have been discovered serendipitously the rational design of the molecules has been attempted from years. However, only the recent years brought a variety of new techniques providing unquestionably efficient procedures. In particular, the methodology of 2D and 3D quantitative structure activity relationships (QSAR) and combinatorial chemistry should be mentioned. In this review the basic methodology of the classical Hansch QSAR aproach has been briefly discussed. In general, classical two-dimensional QSAR fails to distinguish between stereoisomers. This fact inspired the development of the idea of 3D QSAR. Just the last year brought the concept of 4D QSAR covering quantitative description of conformational effects. On the other hand, the comparative molecular field analysis CoMFA, which is the most common 3D QSAR scheme, demands perfect alignment of the series of molecules analyzed. Moreover, the results critically depend upon the way of overlaying the molecules. The CoMFA and 4D QSAR analyses base on the statistical techniques of the partial least square (PLS) and cross-validation procedure. Both from the theoretical and practical points of view more flexible procedures for the alignment of molecules are needed. A comparative technique of self-organizing neutral network provides one of alternatives allowing for such more flexible visualization and quantitative analysis of molecular similarity. The problem of the molecules alignment can also be solved by the use of a new 2D QSAR technique, the so-called holographic QSAR (HQSAR) which uses fragmental coding of the molecule. Combinatorial chemistry is a method that puts together the randomness of screening and the rationality of design. The idea of combinatorial synthesis consists in the parallel synthesis of the set (combinatorial library) of compounds obtained simultaneously. Depending upon the technique used such libraries can be obtained as complex mixtures of the products of the defined composition or separate compounds. Although it is the diversity of molecular library created by combinatorial procedure that allows for increasing the probability of finding active analogs, combinatorial methods are far from brute randomness. The new methods for the description of the similarity of such libraries have been proposed. The newest trend represented by in vitro nucleic acid selection which is designed to mimic the Nature's evolutionary processes is probably one of the most interesting ideas in drug desing. Just recently this idea has been expanded to small organic molecules.