Synthesis and Anticancer Activity of 1,3,4-Thiadiazoles with 3-Methoxyphenyl Substituent

Sara Janowska; Dmytro Khylyuk; Agnieszka Gornowicz; Anna Bielawska; Michał Janowski; Robert Czarnomysy; Krzysztof Bielawski; Monika Wujec

doi:10.3390/molecules27206977

Molecules (Oct 2022)

Synthesis and Anticancer Activity of 1,3,4-Thiadiazoles with 3-Methoxyphenyl Substituent

Sara Janowska,
Dmytro Khylyuk,
Agnieszka Gornowicz,
Anna Bielawska,
Michał Janowski,
Robert Czarnomysy,
Krzysztof Bielawski,
Monika Wujec

Affiliations

Sara Janowska: Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 4a Chodzki Str., 20-093 Lublin, Poland
Dmytro Khylyuk: Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 4a Chodzki Str., 20-093 Lublin, Poland
Agnieszka Gornowicz: Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1 Street, 15-089 Bialystok, Poland
Anna Bielawska: Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1 Street, 15-089 Bialystok, Poland
Michał Janowski: Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 4a Chodzki Str., 20-093 Lublin, Poland
Robert Czarnomysy: Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1 Street, 15-089 Bialystok, Poland
Krzysztof Bielawski: Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1 Street, 15-089 Bialystok, Poland
Monika Wujec: Department of Organic Chemistry, Faculty of Pharmacy, Medical University, 4a Chodzki Str., 20-093 Lublin, Poland

DOI: https://doi.org/10.3390/molecules27206977
Journal volume & issue: Vol. 27, no. 20
p. 6977

Abstract

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Based on the results of previous work, we designed and synthesized 1,3,4-thiadiazole derivatives. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and a normal cell line (fibroblasts). The results showed that all compounds displayed weak anticancer activity towards two breast cancer lines: an estrogen-dependent cell line (MCF-7) and an estrogen-independent cell line (MDA-MB-231). The compound most active towards MCF-7 breast cancer cells was SCT-4, which decreased DNA biosynthesis to 70% ± 3 at 100 µM. The mechanism of the anticancer action of 1,3,4-thiadiazole was also investigated. We choose a set of the most investigated proteins, which are attractive anticancer targets. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds but the most likely mechanism of action for the new compounds is connected with the activity of caspase 8.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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