Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives

@article{Larik2017SyntheticAT,
  title={Synthetic approaches towards the multi target drug spironolactone and its potent analogues/derivatives},
  author={Fayaz Ali Larik and Aamer Saeed and Danish Shahzad and Muhammad Faisal and Hesham R. El‐Seedi and Haroon Mehfooz and Pervaiz Ali Channar},
  journal={Steroids},
  year={2017},
  volume={118},
  pages={76-92}
}
HIGHLIGHTSSynthetic approaches to the versatile mutitarget drug spironolactone have been reviewed.Aims to provide a comprehensive insight to the synthetic endeavors devoted to drug and its analogues/derivatives.It will help the synthetic chemist to design and prepare new more effective derivatives.The efficacy and limitations of the drug have also been discussed. ABSTRACT Spironolactone is a well‐known multi‐target drug and is specifically used for the treatment of high blood pressure and heart… Expand
New oxygen-containing androstane derivatives: Synthesis and biological potential
Abstract New steroidal D-homo androstane derivatives with 5β,6β-epoxy-3,16-dicarbonyl, 6α- and 6β-hydroxy-3,16-dicarbonyl and 3β,5α-dihydroxy-6,16-dicarbonyl moieties were synthesized and confirmedExpand
Applications of Lawesson’s reagent in the synthesis of naturally occurring steroids and terpenoids
TLDR
Among the various thionating reagents, Lawesson’s reagent was found to be most suitable and showed versatile properties, including chemoselectivity and functional group tolerance. Expand
Selective ligands of membrane progesterone receptors as a key to studying their biological functions in vitro and in vivo
TLDR
This review is the first attempt to summarize available data on the structures of compounds interacting with mPRs and analyze them in terms of the differences in binding to membrane and nuclear receptors. Expand
Hexafluoroisopropanol-Mediated Domino Reaction for the Synthesis of Thiazolo-androstenones: Potent Anticancer Agents
TLDR
A cascade reaction of thioamides with 6β-bromoandrostenedione in hexafluoroisopropanol formed substituted thiazolo-androstenones, which are potent growth inhibitors of colon, central nervous system, melanoma, ovarian, and renal cancer cell lines with 50% growth inhibition values as low as 1.04 μM. Expand
Distinct Regioselectivity of Fungal P450 Enzymes for Steroidal Hydroxylation
TLDR
Two P450 enzymes from Thanatephorus cucumeris NBRC 6298 are identified by combination of transcriptome sequencing and heterologous expression in Pichia pastoris and display different regioselectivity of hydroxylation from that of their isoenzyme, CYP5150AP2, which possesses 19- and 11β-hydroxylase activities. Expand
Emerging Targets of Diuretic Therapy
TLDR
The potential advantages and side effects of these potential diuretics, including WNK‐SPAK inhibitors, ClC‐K channel antagonists, ROMKChannel antagonists, and pendrin and urea transporter inhibitors are discussed. Expand
Advances in transition-metal-catalyzed synthesis of 3-substituted isocoumarins
Abstract 3-Substituted isocoumarins are the most abundant class of naturally isocoumarins, found in several biologically active scaffolds and are precursors towards complex natural products.Expand
Spironolactone‐induced XPB degradation depends on CDK7 kinase and SCFFBXL18 E3 ligase
TLDR
It is found that the Ser90 residue of XPB is essential for the chemical‐induced destabilization, which led to a model that spironolactone may trigger the phosphorylation ofXPB at Ser90 by CDK7, which promotes the recognition and polyubiquitination of XPBs by SCFFBXL18 for proteasomal degradation. Expand
Effects of spironolactone on hypoxia-inducible factor-1α in the patients receiving coronary artery bypass grafting.
TLDR
Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardia remodeling and preventing atrial fibrillation. Expand
Photocurable Bioinks for the 3D Pharming of Combination Therapies
TLDR
The potential of material jetting in conjunction with binder jetting techniques (powder-bed 3D printing), for the production of combination therapy oral dosage forms involving both hydrophilic and hydrophobic drugs is confirmed. Expand
...
1
2
...

References

SHOWING 1-10 OF 119 REFERENCES
Three new epoxy-spirolactone derivatives: characterization in vivo and in vitro.
TLDR
It appears that the 9 alpha, 11 alpha-position of the steroid structure is a site of the molecule which can be modified to improve the specificity of aldosterone-antagonists not only in vitro, but also in vivo. Expand
Antiandrogenic effect of spirolactones: mechanism of action.
TLDR
It seems likely that spirolactones, besides their action on testosterone biosynthesis, exert their antiandrogenic activity via a peripheral androgen antagonism. Expand
SC 25152: a potent mineralocorticoid antagonist with decreased antiandrogenic activity relative to spironolactone.
TLDR
It is demonstrated that the antiandrogenic and antimineralocorticoid activities of spironolactone analogs can be dissociated and the utility of measurements of drug-receptor interaction to identify a compound with desired pharmacological properties is illustrated. Expand
Synthesis of two new hydroxylated derivatives of spironolactone by microbial transformation.
TLDR
Two new hydroxylated derivatives of spironolactone were synthesized and their structures were characterized on the basis of the spectroscopic data and can be efficiently converted into the products within 72 h after its addition to the fermentation broth of C. elegans ATCC 9245. Expand
Identification of spironolactone metabolites in plasma and target organs of guinea pigs.
TLDR
Data suggest that TM is principally responsible for the renal antimineralocorticoid effects of SL and support the purported role of TH in the degradation of testicular cytochrome P-450. Expand
Spironolactone-related inhibitors of type II 17beta-hydroxysteroid dehydrogenase: chemical synthesis, receptor binding affinities, and proliferative/antiproliferative activities.
TLDR
It was found that a para-substituted benzylthio group at the 7alpha-position enhances the inhibitory potency of spironolactone derivatives on type II 17beta-HSD, and offer an interesting tool to study the regulation of this enzyme in several biological systems. Expand
A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone
TLDR
This procedure synthesized this metabolite by thioalkylation of 7α-thio spironolactone using Hünig's base with a very good yield and used this procedure to prepare, with an easy work-up and high yields, 7α -thioether and thioester derivatives of spironlactone that could be useful for further Structure-Activity Relationships studies. Expand
Aldosterone antagonists in hypertension and heart failure.
TLDR
In vitro and in vivo evidences suggest that aldosterone promotes myocardial fibrosis, and ARA have been proposed as complementary treatment associated to ACE inhibitors and angiotensin receptor antagonists. Expand
Spironolactone, eplerenone and the new aldosterone blockers in endocrine and primary hypertension.
TLDR
A narrative review summarizes the knowledge on the use of classic MRAs in hypertension and covers the evidence currently available on new aldosterone blockers. Expand
Advances in development of inhibitors of 17beta hydroxysteroid dehydrogenases.
  • D. Poirier
  • Chemistry, Medicine
  • Anti-cancer agents in medicinal chemistry
  • 2009
TLDR
In conclusion, the present review article gives a description of novel inhibitors of 17beta-HSD that were published in 2003-2006 that could be used to block the degradation of estradiol, an attractive strategy for treating osteoporosis and Alzheimer's disease. Expand
...
1
2
3
4
5
...