Bioorganic & Medicinal Chemistry Reports

A scientific open access journal in the field of Bioorganic and Medicinal Chemistry
Editor in Chief: Oztekin Algul
Managing Editor: Ahmet C Goren

LATEST ARTICLES

Original Article

New molecule design with in-silico methods for Covid-19 treatment

Bioorg. Med. Chem. Rep. (2020) 3:2 ; 32 - 40
by Mehmet Abdullah Alagöz

Intensive studies are being conducted to develop effective prevention and treatment strategies for the Covid-19 pandemic. During a pandemic, it is vital to act quickly to develop a defense strategy. It usually takes a long time to develop a preventive vaccine, and immediate drug development is needed to reduce the impact of the rapidly increasing Covid-19 pandemic. This study aimed to design an effective and potent drug by selecting remdesivir, a nucleotide analog prodrug that inhibits viral RNA polymerases and is known to be active against Covid-19. Remdesivir is metabolized into active nucleoside triphosphate (NTP) by the host; this metabolite competes with adenosine triphosphate (ATP) for incorporation into the nascent RNA strand. Therefore, molecular docking studies have been conducted based on NTP (the active form of remdesivir), and a target molecule that could be effective against Covid-19 has been designed.

DOI
http://doi.org/10.25135/acg.bmcr.23.20.08.1773
Keywords
SARS-CoV-2 , Covid-19 remdesivir molecular docking
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© 2020 ACG Publications. All rights reserved.
Original Article

Synthesis and biological evaluation of 1,3,5-triazine-substituted ureido benzenesulfonamides as antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitors

Bioorg. Med. Chem. Rep. (2020) 3:2 ; 22 - 31
by Nebih Lolak , Muhammed Tuneg , Aslınur Doğan , Mehmet Boğa and Suleyman Akocak

A series of twenty 1,3,5-triazine-substituted ureido benzenesulfonamides 2 (a-e) and 3 (a-o) were re-synthesized and assayed for antioxidant properties by using several different methods including 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging assay, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation radical decolarization assay, metal chelating and cupric reducing antioxidant capacity (CUPRAC) methods.  The inhibitory effects of compounds on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes have been also demonstrated. All compounds showed a greater antioxidant capacity against ABTS assay by having a more potent activity than the standards BHT, BHA and α-TOC. In general, all compounds were non susceptible to against AChE enzyme. On the other hand, several lead compounds were obtained from the current series against BChE enzyme. More specifically, compound 3m showed great inhibition profile against BChE with % inhibition value of 93.77, which is better than the standard drug galantamine (% inhibition value of 87.86).

DOI
http://doi.org/10.25135/acg.bmcr.22.20.07.1706
Keywords
1,3,5-triazine; sulfonamide acetylcholinesterase butyrylcholinesterase antioxidant
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© 2020 ACG Publications. All rights reserved.
Original Article

Alicyclic diamide derivatives as potential anticancer agents

Bioorg. Med. Chem. Rep. (2020) 3:1 ; 15 - 21
by Burak Kuzu and Ceylan Hepokur

The present study was carried out in the attempt to design a new class of potential anticancer agents comprising sixteen compounds (10-25) sharing the alicyclic diamide as a core. Their biological potential towards breast cancer was tested by using MTT assay on breast cancer (MCF-7)and non-tumorigenic breast (MCF-10-2A)cell lines. Screening results show that the anti-proliferative effects of compounds (13, 19 and 20) correlate with the lipophilicity and selectivity of compounds. Interestingly, the active compounds distinguished from others with a quite high selectivity value that is comparable to 5-FU. Therefore, new small molecules containing alicyclic diamide fragments will have a significant contribution to the development of new era anticancer drug candidates for breast cancer.

DOI
http://doi.org/10.25135/acg.bmcr.21.20.05.1666
Keywords
Phenyl alicyclic diamides breast cancer anti-proliferative anti-cancer
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© 2020 ACG Publications. All rights reserved.
Discussion Article

Telomere, telomerase and telomerase inhibitors

Bioorg. Med. Chem. Rep. (2020) 3:1 ; 1 - 14
by Yusuf Ataker and Rahime Şimşek

Telomeres are DNA sequences with protective structure which are located at the ends of chromosomes. It is known that the telomere length is shortening after all cleavage in somatic cells, whereas in tumor cells this shortening does not occur, and the telomere length is protected. Telomerase is a DNA polymerase with a special structure. The components of its structure are hTR, hTERT and TP1. hTR and hTERT are the components that play a major role in providing continuity to the chromosome. In normal cells, there is almost no telomerase enzyme activity, except for germ cells and stem cells. On the other hand, 85-90 % of cancer cell and cancer cell lines highly express telomerase. Expression of telomerase enzyme contributes to the development of cancer cells. This situation makes telomerase an interesting structure for cancer treatment and it is also supposed that the compounds that target telomerase could be effective in anticancer treatment. Telomerase inhibitors cause apoptosis and cell aging as a result of the shortening of telomere length in telomerase positive cancer cells. In this study, together with the function of the telomerase enzyme, hTERT target inhibitors, hTR target inhibitors, gene and immune treatments directed to telomerase, as well as other telomerase inhibitor strategies in treatment were investigated.

DOI
http://doi.org/10.25135/acg.bmcr.20.20.06.1686
Keywords
Telomere telomerase telomerase inhibitor hTERT hTR anticancer
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© 2020 ACG Publications. All rights reserved.