Publications by authors named "Dawid Maliszewski"

4 Publications

  • Page 1 of 1

1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors.

Molecules 2021 Jun 28;26(13). Epub 2021 Jun 28.

Department of Organic Chemistry, Medical University, Mickiewicza Street 2a, 15-222 Białystok, Poland.

A series of new analogs of nitrogen mustards (-) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and -secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman's colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds and , with an inhibitory concentration of AChE IC = 0.051 µM; 0.055 µM and BACE1 IC = 9.00 µM; 11.09 µM, respectively.
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http://dx.doi.org/10.3390/molecules26133942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271926PMC
June 2021

Trimethoprim: An Old Antibacterial Drug as a Template to Search for New Targets. Synthesis, Biological Activity and Molecular Modeling Study of Novel Trimethoprim Analogs.

Molecules 2019 Dec 27;25(1). Epub 2019 Dec 27.

Department of Organic Chemistry, Medical University of Bialystok, 15222 Bialystok, Poland.

A new series of trimethoprim (TMP) analogs containing amide bonds (-) have been synthesized. Molecular docking, as well as dihydrofolate reductase (DHFR) inhibition assay were used to confirm their affinity to bind dihydrofolate reductase enzyme. Data from the ethidium displacement test showed their DNA-binding capacity. Tests confirming the possibility of DNA binding in a minor groove as well as determination of the association constants were performed using calf thymus DNA, T4 coliphage DNA, poly (dA-dT) and poly (dG-dC). Additionally, the mechanism of action of the new compounds was studied. In conclusion, some of our new analogs inhibited DHFR activity more strongly than TMP did, which confirms, that the addition of amide bonds into the analogs of TMP increases their affinity towards DHFR.
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http://dx.doi.org/10.3390/molecules25010116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983048PMC
December 2019

Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.

J Antibiot (Tokyo) 2020 01 2;73(1):5-27. Epub 2019 Oct 2.

Department of Organic Chemistry, Medical University of Białystok, Mickiewicza Street 2a, 15-222, Białystok, Poland.

The development of new mechanisms of resistance among pathogens, the occurrence and transmission of genes responsible for antibiotic insensitivity, as well as cancer diseases have been a serious clinical problem around the world for over 50 years. Therefore, intense searching of new leading structures and active substances, which may be used as new drugs, especially against strain resistant to all available therapeutics, is very important. Dihydrofolate reductase (DHFR) has attracted a lot of attention as a molecular target for bacterial resistance over several decades, resulting in a number of useful agents. Trimethoprim (TMP), (2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine) is the well-known dihydrofolate reductase inhibitor and one of the standard antibiotics used in urinary tract infections (UTIs). This review highlights advances in design, synthesis, and biological evaluations in structural modifications of TMP as DHFR inhibitors. In addition, this report presents the differences in the active site of human and pathogen DHFR. Moreover, an excellent review of DHFR inhibition and their relevance to antimicrobial and parasitic chemotherapy was presented.
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http://dx.doi.org/10.1038/s41429-019-0240-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102388PMC
January 2020

Synthesis and cellular effects of novel 1,3,5-triazine derivatives in DLD and Ht-29 human colon cancer cell lines.

Invest New Drugs 2020 08 13;38(4):990-1002. Epub 2019 Sep 13.

Department of Organic Chemistry, Medical University of Bialystok, Białystok, Poland.

This study provides new information on the cellular effects of 1,3,5-triazine nitrogen mustards with different peptide groups in DLD and Ht-29 human colon cancer cell lines. A novel series of 2,4,6-trisubstituted 1,3,5-triazine derivatives bearing 2-chloroethyl and oligopeptide moieties was designed and synthesized. The most cytotoxic derivative was triazine with an Ala-Ala-OMe substituent on the ring (compound 7b). This compound induced time- and dose-dependent cytotoxicity in the DLD-1 and HT-29 colon cancer cell lines. The triazine derivative furthermore induced apoptosis through intracellular signaling pathway attenuation. Compound 7b may be a candidate for further evaluation as a chemotherapeutic agent against colorectal cancer.
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http://dx.doi.org/10.1007/s10637-019-00838-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340680PMC
August 2020
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