Research Article

Synthesis, in vitro and in silico anticancer evaluation of novel pyridin-2-yl estra-1,3,5(10)-triene derivatives

https://orcid.org/0000-0003-1961-737X

Department of Chemistry, Biochemistry & Environmental Protection, University of Novi Sad, Faculty of Sciences, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia

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Sofija S Bekić

https://orcid.org/0000-0002-9020-698X

Department of Chemistry, Biochemistry & Environmental Protection, University of Novi Sad, Faculty of Sciences, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia

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Edward T Petri

https://orcid.org/0000-0002-3650-1523

Department of Biology & Ecology, University of Novi Sad, Faculty of Sciences, Trg Dositeja Obradovića 2, 21000 Novi Sad, Serbia

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Andjelka S Ćelić

https://orcid.org/0000-0002-1058-6872

Department of Biology & Ecology, University of Novi Sad, Faculty of Sciences, Trg Dositeja Obradovića 2, 21000 Novi Sad, Serbia

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Dimitar S Jakimov

https://orcid.org/0000-0002-1747-4718

Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put Dr Goldmana 4, 21204 Sremska Kamenica, Serbia

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Marija N Sakač

https://orcid.org/0000-0002-2796-1296

Department of Chemistry, Biochemistry & Environmental Protection, University of Novi Sad, Faculty of Sciences, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia

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Ivana Z Kuzminac

*Author for correspondence:

E-mail Address: ivana.kuzminnac@dh.uns.ac.rs

https://orcid.org/0000-0001-8045-3568

Department of Chemistry, Biochemistry & Environmental Protection, University of Novi Sad, Faculty of Sciences, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia

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Published Online:17 Apr 2024https://doi.org/10.4155/fmc-2024-0039

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Abstract

Aim: The aim of this study was the synthesis of steroid compounds with heterocyclic rings and good anticancer properties. Materials & methods: The synthesis, in silico and in vitro anticancer testing of novel pyridin-2-yl estra-1,3,5(10)-triene derivatives was performed. Results: All synthesized compounds have shown promising results for, antiproliferative activity, relative binding affinities for the ligand binding domains of estrogen receptors α, β and androgen receptor, aromatase binding potential, and inhibition of AKR1C3 enzyme. Conclusion: 3-Benzyloxy (17E)-pycolinilidene derivative 9 showed the best antitumor potential against MDA-MB-231 cell line, an activity that can be explained by its moderate inhibition of AKR1C3. Molecular docking simulation indicates that it binds to AKR1C3 in a very similar orientation and geometry as steroidal inhibitor EM1404.

Tweetable abstract

The series of pyridine-containing estra-1,3,5(10)-triene derivatives was synthesized. One novel derivative stood out by its excellent activity against the MDA-MB-231 cell line. This activity can be explained by its moderate inhibition of the AKR1C3 enzyme.

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Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Received 1 February 2024

Accepted 26 March 2024

Published online 17 April 2024

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To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/fmc-2024-0039

Author contributions

Conception, drafting or design of the work and revising it critically for important intellectual content: I Kuzminac; acquisition and analysis M Stevanović, S Bekić, D Jakimov and E Petri; interpretation of data for the work: I Kuzminac, M Stevanović, A Ćelić and E Petri; drafting the work and revising it critically for important intellectual content: E Petri and M Sakač.

Financial disclosure

The authors acknowledge the financial support of Provincial Secretariat for Higher Education and Scientific Research of the Autonomous Province of Vojvodina [Project: New steroid derivatives – potential chemotherapeutics, No. 142-451-3463/2023-01] and the Ministry of Science, Technological Development and Innovation of the Republic of Serbia [Grant No. 451-03-66/2024-03/200125 and 451-03-65/2024-03/200125]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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No writing assistance was utilized in the production of this manuscript.

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