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

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2032
Author(s):  
Vanessa Brito ◽  
Gilberto Alves ◽  
Paulo Almeida ◽  
Samuel Silvestre

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.

2020 ◽  
Vol 20 (21) ◽  
pp. 1938-1949 ◽  
Author(s):  
Dan Xu ◽  
Zhi Xu

Indole alkaloids, which are abundant in nature, are a significant source of pharmacologically active compounds. Indole alkaloids have the potential to exert anticancer activity via various antiproliferative mechanisms, and some of them, such as Vinblastine and Vincristinem, have already used in clinics or under clinical evaluations for the treatment of cancers. Therefore, indole alkaloids occupy an important position in the discovery of novel anticancer agents. This review emphasizes the recent development of indole alkaloids as potential anticancer agents, their structure-activity relationship, and mechanisms of action covering the articles published from 2015 to 2020.


1979 ◽  
Vol 10 (29) ◽  
Author(s):  
A. N. GRINEV ◽  
N. V. ARKHANGEL'SKAYA ◽  
G. YA. URETSKAYA ◽  
A. A. STOLYARCHUK ◽  
P. A. GALENKO-YAROSHEVSKII

2021 ◽  
Vol 10 ◽  
Author(s):  
Thom Browne ◽  
Mark S. Gold ◽  
David M. Martin

Background: Globally, an alarming number of pharmaceutically active compounds are now routinely added to the street drugs of abuse, cocaine and heroin. In some cases, seventeen (17) or more potentially toxic compounds are found in a single street purchased bag or block of cocaine or heroin. Pharmacologically active compounds, impurities, or breakdown products from drug manufacturing and industrial chemicals (collectively referred to as toxic adulterants) are now found in street drugs. They include, but are not limited to: antipsychotics, antidepressants, anxiolytics, antihistamines, anthelminthics, anesthetics, anti-inflammatorys, antipyretics, analgesics, antispasmodics, antiarrhythmics, antimalarials, veterinary medications, broncho-dilators, expectorants, sedatives, muscle relaxers, natural/synthetic hallucinogens, decongestants, new psychoactive substanc-es (NPS), industrial compounds, fungicides, and impurities in the manufacturing process. All can be found within a single street purchase of heroin or cocaine. Routine clinical or workplace drug testing will not detect all these toxic adulterants. Only specialty forensic tests, specifically ordered, will detect them. The synergistic effect on the human body of such an unprece-dented combination of pharmacologically active compounds is unknown and potentially deadly. This is especially seen in daily abusers who are exposed to these combinations multiple times a day over an extended period of time. Individuals with substance use disorders (SUDs) have several co-occurring health problems that make them more susceptible to Covid-19, including compromised immune, pulmonary, cardiovascular, and respiratory systems. These problems are high-risk factors for the acquisition of Covid-19 infection and more serious complications from the virus, including hospitalization and death. Objective: To bring to the attention of public health officials, addiction medicine specialists, treatment officials, therapists, and the general public the alarming increase of dangerous toxic adulterants being added to street drugs and their potentially lethal synergistic effects. Also, to provide insights into how these new formulations can have serious pathophysiological effects on individuals with Substance Abuse Disorders (SUDs) during the COVID-19 pandemic. Method: The literature on street drug cutting agents, toxic adulterants, NPS, manufacturing byproducts, and other industrial compounds will be reviewed. Also a review of the literature of pathophysiological effects, especially on SUD patients, in light of the COVID-19 pandemic will be presented. This is combined with international and USA studies that were carried out by the Colombo Plan that identified these new combinations of toxic adulterants in street drugs, using state of the art field and forensic laboratory detection technologies. Results: The majority of street drugs, in some cases more than ninety-five percent, now have multiple toxic adulterants. It is rare that a street purchase of cocaine or heroin does not contain multiple toxic adulterants, cutting agents, NPS, manufactur-ing byproducts, or industrial chemicals. Conclusion: This dangerous new composition in world street drug supply is unprecedented and may be the undetected cause of many psychostimulant and opioid overdose deaths, as many toxic adulterants are not routinely tested in post-mortem or street drug seizure cases. In addition, several of these toxic adulterants create a catastrophic drop in white blood cells, causing neutropenia and making the abusers susceptible to a wide range of opportunistic infections, including COVID-19. This pro-found change in the world street drug supply has catastrophic implications for individuals with SUDs and our health care system, especially in the era of the COVID-19 pandemic.


2020 ◽  
Vol 21 (22) ◽  
pp. 8692
Author(s):  
Alessandra Benassi ◽  
Filippo Doria ◽  
Valentina Pirota

Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles—five-membered aromatic rings—emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazole-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins, and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.


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