Highlights on Steroidal Arylidene Derivatives as a Source of Pharmacologically Active Compounds: A Review

Abstract

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Additionally, steroids have been associated with a relatively low toxicity and high bioavailability. Nowadays, multiple steroidal derivatives are clinically available for the treatment of numerous diseases. Moreover, different structural modifications on their skeleton have been explored, aiming to develop compounds with new and improved pharmacological properties. Thus, steroidal arylidene derivatives emerged as a relevant example of these modifications. This family of compounds has been mainly described as 17β-hydroxysteroid dehydrogenase type 1 and aromatase inhibitors, as well as neuroprotective and anticancer agents. Besides, due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems. In fact, starting from arylidenesteroids, it was possible to develop bioactive steroidal pyrazolines, pyrazoles, pyrimidines, pyridines, spiro-pyrrolidines, amongst others. Most of these products have also been studied as anti-inflammatory and anticancer agents, as well as 5α-reductase and aromatase inhibitors. This work aims to provide a comprehensive overview of steroidal arylidene derivatives described in the literature, highlighting their bioactivities and importance as synthetic intermediates for other pharmacologically active compounds.

Arylidene and amino spacer‐linked rhodanine‐quinoline hybrids as upgraded antimicrobial agents

“…Especially in drug discovery processes, linker hybrids have a notable impact because of their excellent binding affinity with DNA active sites and cell membranes of drug‐sensitive and drug‐resistance microorganisms (Verma et al, 2022). As mentioned above, arylidene rhodanine‐based clinically approved drug candidates target the various Zmp1 enzymes through binding DNA gyrase and inhibiting DNA replication and transcription (Brito et al, 2021; Maddila et al, 2020). However, amino spacer linkers, in which nitrogen units immediately bind with the active site of nitrogen‐based amino acids of microbial pathogens and decrease the growth of the bacterial cells (Oh et al, 2021).…”

Synthesis, In Vitro Biological Evaluation of Antiproliferative and Neuroprotective Effects and In Silico Studies of Novel 16E-Arylidene-5α,6α-epoxyepiandrosterone Derivatives

“…Within this group, steroidal arylidene derivatives, principally those bearing heteroatoms or halogens on their structures, have been mainly reported as 17β-HSD type 1 inhibitors, as well as anti-inflammatory and antiproliferative agents [ 14 , 15 , 16 , 17 , 18 , 19 ]. Additionally, 16 E -arylideneandrostane derivatives have been reported as potent anti-cancer agents (a representative example is shown in Figure 1 ), being potentially useful in the treatment of leukemia, breast and prostate cancer, and brain tumors [ 15 ].…”

Diols Speed Up Guanidine Base Catalyzed Claisen‐Schmidt Condensation to Produce New 15‐Arylidene Steroids

“…[3] Arylidene steroids, important representatives of the compounds mentioned before, were reported to possess a wide range of interesting pharmacological properties, including antifungal, antimicrobial, antioxidant, anti-arrhythmic, anticancer, antimalarial, and anti-inflammatory effect. [4] Anticancer activity is often related to the inhibition of different enzymes of synthetic pathways towards steroid hormones, [5] but other mechanisms, such suppression of tumour angiogenesis [6] or activation of apoptotic pathways [7] were also reported. Besides, some arylidene derivatives were shown to alleviate lipopolysaccharide-induced neurodegenerative disorders [8] or can be promising neuroprotective agents for the treatment of Alzheimer's and Parkinson's diseases.…”

“…Claisen-Schmidt condensation of the readily available steroidal ketones and aromatic aldehydes, yielding arylidine steroids, was performed using different catalysts, such as lithium diisopropylamide (LDA), [12] KF/Al 2 O 3 , [13] I 2 -Al 2 O 3 [14] or, most commonly, alkali-hydroxides. [4] Some of the reactions were found to be accelerated by microwave irradiation. [14,15] Some recent studies offer the perspective of more efficient catalysts for the condensation reaction.…”

“…that exert diverse biological activity, including antimicrobial, antioxidant and antitumor effect [3] . Arylidene steroids, important representatives of the compounds mentioned before, were reported to possess a wide range of interesting pharmacological properties, including antifungal, antimicrobial, antioxidant, anti‐arrhythmic, anticancer, antimalarial, and anti‐inflammatory effect [4] . Anticancer activity is often related to the inhibition of different enzymes of synthetic pathways towards steroid hormones, [5] but other mechanisms, such suppression of tumour angiogenesis [6] or activation of apoptotic pathways [7] were also reported.…”