Heterocyclic androstane and estrane d-ring modified steroids: Microwave-assisted synthesis, steroid-converting enzyme inhibition, apoptosis induction, and effects on genes encoding estrogen inactivating enzymes

Kulmány, Ágnes; Herman, Bianka Edina; Zupkó, István; Sinreih, Maša; Rižner, Tea Lanišnik; Savić, Marina P.; Oklješa, Aleksandar M.; Nikolić, Andrea R.; Nagy, Viktória; Ocsovszki, Imre; Szécsi, Mihály; Јovanović-Šanta, Suzana

doi:10.1016/j.jsbmb.2021.105997

Cited by 8 publications

(4 citation statements)

References 62 publications

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“…The introduction of the nitrile functional group at the aldehyde can be achieved via the intermediate tosyl‐hydrazone, as described by Marczak and Wicha [52] . Starting from the D‐secoaldehyde 1 [53] via p ‐toluenesulfonyl hydrazone derivative 9 [54] the compound 10 was synthesized. Further reaction of compound 10 with Jones reagent at the room temperature gave 6,7‐seco‐6,7‐dioic acid 11 .…”

Section: Resultsmentioning

confidence: 99%

A Search for Sars‐CoV‐2 Main Protease Inhibitors: Synthesis and Docking Study of Steroidal Dinitriles

Nikolić,

Kuzminac,

Petri

et al. 2024

ChemistrySelect

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Coronaviruses are continually evolving, as evidenced by the emergence of three closely related pathogenic variants over the past two decades: SARS (2002), MERS (2012), and SARS‐CoV‐2 (2019); and the appearance of many new SARS‐CoV‐2 strains during the COVID‐19 pandemic. Hence, COVID‐19 has now become a pandemic disease; with a real possibility for the emergence of new deadly SARS‐related coronaviruses. The SARS‐CoV‐2 main protease, Mpro is an attractive drug target for the development of inhibitors against SARS type and other coronaviruses because it is essential for the viral life cycle and highly conserved among a wide range of pathogenic coronaviruses. This motivated the synthesis of novel inhibitors of Mpro, which could be the basis for COVID‐19 drug development. The synthesis of new 5,6 : 16,17‐diseco and 6,7 : 16,17‐disecoandrostane 16,17a‐dinitriles is reported. In silico ADMET analyses suggest that the synthesized compounds possess drug‐like properties with no predicted toxicities. Structural similarity analyses indicates that synthesized B,D‐diseco 16,17a‐dinitrile derivatives have potential as protease inhibitors. Molecular docking simulations suggest that B,D‐diseco 16,17a‐dinitriles could inhibit substrate binding by Mpro. The present study suggests that newly synthesized androstane 5,6 : 16,17‐diseco‐5‐keto‐6‐oic acid and 6,7 : 16,17‐diseco‐6,7‐dioic acid 16,17a‐dinitriles 8 and 11 could represent a starting point for the design of Mpro inhibitors against SARS type coronaviruses.

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Section: Resultsmentioning

confidence: 99%

A Search for Sars‐CoV‐2 Main Protease Inhibitors: Synthesis and Docking Study of Steroidal Dinitriles

Nikolić,

Kuzminac,

Petri

et al. 2024

ChemistrySelect

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“…Steroidal compounds have been associated with antitumor activity for many years. Several reports focusing on their interesting properties as anticancer agents have been published [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The oxyimino group of oxime compounds is also a structural feature that confers very interesting biological properties among them antitumor activity [ 7 , 34 ].…”

Section: Steroidal Oximes As Antitumor Agentsmentioning

confidence: 99%

The Structural Diversity and Biological Activity of Steroid Oximes

et al. 2023

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Steroids and their derivatives have been the subject of extensive research among investigators due to their wide range of pharmacological properties, in which steroidal oximes are included. Oximes are a chemical group with the general formula R1R2C=N−OH and they exist as colorless crystals and are poorly soluble in water. Oximes can be easily obtained through the condensation of aldehydes or ketones with various amine derivatives, making them a very interesting chemical group in medicinal chemistry for the design of drugs as potential treatments for several diseases. In this review, we will focus on the different biological activities displayed by steroidal oximes such as anticancer, anti-inflammatory, antibacterial, antifungal and antiviral, among others, as well as their respective mechanisms of action. An overview of the chemistry of oximes will also be reported, and several steroidal oximes that are in clinical trials or already used as drugs are described. An extensive literature search was performed on three main databases—PubMed, Web of Science, and Google Scholar.

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“…These compounds have shown good bioavailability, antiproliferative activity, and inhibition of various en- The structure of testolactone and its biological activity were one of the motives in the design of a series of D-homo lactone steroids for our research group. 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].…”

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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Heterocyclic androstane and estrane d-ring modified steroids: Microwave-assisted synthesis, steroid-converting enzyme inhibition, apoptosis induction, and effects on genes encoding estrogen inactivating enzymes

Cited by 8 publications

References 62 publications

A Search for Sars‐CoV‐2 Main Protease Inhibitors: Synthesis and Docking Study of Steroidal Dinitriles

A Search for Sars‐CoV‐2 Main Protease Inhibitors: Synthesis and Docking Study of Steroidal Dinitriles

The Structural Diversity and Biological Activity of Steroid Oximes

Testolactone: The Rise and Fall of a Drug

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