Synthesis and anticancer potential of novel 5,6-oxygenated and/or halogenated steroidal d-homo lactones

Kuzminac, Ivana; Jakimov, Dimitar; Bekić, Sofija S.; Ćelić, Andjelka; Marinović, Maja; Savić, Marina P.; Raičević, Vidak; Kojić, Vesna; Sakač, Marija N.

doi:10.1016/j.bmc.2020.115935

Cited by 16 publications

(2 citation statements)

References 62 publications

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“…These compounds have shown good bioavailability, antiproliferative activity, and inhibition of various enzymes involved in steroidogenesis [129][130][131][132][133][134]. Among the significant number of structures, compounds presented in Figure 8 stand out for their antiproliferative activity against different tumor cell lines [135][136][137][138][139]. High activity against estrogen-negative breast cancer cells (MDA-MB-231) was observed for compounds 50 (2.09 µM), 51 (9.30…”

Section: Biologically Active Derivatives and Analogs Of Testolactonementioning

confidence: 99%

Testolactone: The Rise and Fall of a Drug

Savić

Kuzminac

Nikolić

2023

DDC

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Testolactone is structurally related to testosterone and belongs to the first generation of aromatase inhibitors. It is a non-selective irreversible aromatase enzyme inhibitor that was one of the first steroids used in the clinical treatment of breast cancer. The use of testolactone in the treatment of breast cancer started in 1970, although its ability to inhibit aromatase was not discovered until 1975. Its use was primarily based on the inhibition of estrogen synthesis, which was applied in the treatment of estrogen-dependent breast cancers, in the treatment of disorders of sex steroid excess, familial male-limited precocious puberty, or in the treatment of patients with McCune–Albright syndrome, etc. The weak inhibitory activity of testolactone, and the moderate clinical response, prevented its widespread use, which ultimately resulted in withdrawal from the drug market in 2008. This review paper is dedicated to testolactone, its rise in the second half of the 20th century, and its fall in the first decade of the 21st century. Regardless of withdrawal from the market, for many years testolactone was a drug that improved the quality of life of patients facing one of the most serious diseases today, and for this reason, this paper describes medicinal application, synthesis, and modifications of testolactone.

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Section: Biologically Active Derivatives and Analogs Of Testolactonementioning

confidence: 99%

Testolactone: The Rise and Fall of a Drug

Savić

Kuzminac

Nikolić

2023

DDC

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“…[32] Quite a few steroids can act as anticancer agents, with modes of action that involve enzymes, receptors, or other non-hormonal mechanisms; [33,34] some of such compounds were prepared by our group. [35][36][37][38][39] Ferrocene-steroid conjugates are molecules in which the steroid scaffold and ferrocene core are bound together with or without the use of a linker group; such compounds are too of great interest in the medicinal chemistry of ferrocene, particularly as potential, selective anticancer drugs. Ferrocenes vectorized with biomolecules were already a subject of extensive reviews.…”

Section: Introductionmentioning

confidence: 99%

Toward Selective Anticancer Agents: Ferrocene‐Steroid Conjugates

Raičević

Radulović²,

Sakač

2022

Eur J Inorg Chem

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The medicinal chemistry of ferrocene is a diverse and rapidly growing field. In the search for selective and more efficient anticancer drugs, ferrocene‐steroid conjugates were explored in the past as a tool to target hormone‐dependent cancer cells, notably those of breast and prostate cancers. The mechanisms by which ferrocene compounds induce cytotoxicity are first examined, as well as how they can be exploited to design conjugates of ferrocene with steroid hormones potentially acting as selective antineoplastics. We sought to cover all relevant literature related to ferrocene‐steroid conjugates, from early works published in the 1970s up to now. Particular attention was bestowed upon research where the conjugates were tested for their antitumor potential.

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Synthesis, anticancer evaluation, and molecular docking study of novel 4‐hydroxybenzo[h][1,6]naphthyridine‐2,5‐dione derivatives

Mostafa

2022

J of Physical Organic Chem

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An operationally efficient and affordable lactone-to-lactam transformation was designed from pyrano [3,2-c]quinolinone 1 to obtain 4-hydroxybenzo [h][1,6] naphthyridine-2,5-dione 2 utilizing ammonium acetate. The newly synthesized compound 2 was subjected to different electrophilic substitution reactions such as nitration, chlorination, bromination, and N-acylation to obtain novel benzo [h][1,6]naphthyridine derivatives with different substituents at C-3, C-4, and NH. Structures of novel products were achieved by elemental analyses and spectroscopic techniques. The benzonapthyridine derivatives were screened for their antitumor activities against some cancer cell lines including HepG-2, HCT-116, and MCF-7. All the examined compounds revealed strong, good, moderate to weak anticancer activity compared with 5-fluorouracil as a reference standard. Compound (3, -3NO 2 ) was the most cytotoxic one and exhibited a higher inhibitory activity than the standard drug against HCT-116 and MCF-7 with IC 50 values of 20.7 ± 1.9 and 22.5 ± 2.1 μg/ml, respectively, and strong activity against HepG-2 with IC 50 = 15.3 ± 0.7 μg/ml. Moreover, a molecular docking study was carried out for the tested compounds against the crystallographic structure of the Topo II enzyme as a potential target to investigate their binding modes. Docking results showed that compound 6b fitted well into the active site of topoisomerase II (PDB ID: 1ZXM) with hydrogen bond interactions.

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Synthesis and anticancer potential of novel 5,6-oxygenated and/or halogenated steroidal d-homo lactones

Cited by 16 publications

References 62 publications

Testolactone: The Rise and Fall of a Drug

Testolactone: The Rise and Fall of a Drug

Toward Selective Anticancer Agents: Ferrocene‐Steroid Conjugates

Synthesis, anticancer evaluation, and molecular docking study of novel 4‐hydroxybenzo[h][1,6]naphthyridine‐2,5‐dione derivatives

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