Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents

Shi, Yun-Kai; Wang, Bo; Shi, Xiaoli; Zhao, Yuan-Di; Yu, Bin

doi:10.1016/j.ejmech.2017.12.094

Cited by 38 publications

(12 citation statements)

References 29 publications

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“…Inactivation of the AR also in castration resistant PCa seems to be therefore a key target of treatment. Current therapeutics include steroidal and non-steroidal anti androgens targeting typically LBD of AR [90][91][92] . Although other modulators targeting another domain are speedily investigated and shows beneficial preclinical profiles [84,93] .…”

Section: Androgen Receptor (Ar) Inhibitormentioning

confidence: 99%

“…Although other modulators targeting another domain are speedily investigated and shows beneficial preclinical profiles [84,93] . Shi et al [92] developed and synthesized a series of steroidal pyridines derivative through the base promoted three component reaction and preliminarily evaluated for their anti-proliferative activity against cancer cell lines. SARs studies displayed that the 4th position of the pyridine ring were chosen over the phenyl rings for the activity.…”

Section: Androgen Receptor (Ar) Inhibitormentioning

confidence: 99%

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Pyridine Moiety: Recent Advances in Cancer Treatment

Sahu¹,

Mishra²,

Kumar³

et al. 2021

ijps

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Pyridine is an imperative pharmacophore, a privileged scaffold and an exceptional heterocyclic system in the field of drug discovery which provides many opportunities in study/explore this moiety as an anticancer agent by acting on various receptors of utmost importance. Several pyridine derivatives are reported to inhibit tubulin polymerization, androgen receptors, human carbonic anhydrase, kinase, topoisomerase enzyme and many other targets for controlling and curing global health issue of cancer. Now a days in combination with other moieties researchers are focusing for development of pyridine new entities for the treatment of cancer. This review throws light on recent biological expansions of pyridine along with their structure activity relationships/molecular docking to deliver association between various synthesized newer derivatives and receptor sites.

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Section: Androgen Receptor (Ar) Inhibitormentioning

confidence: 99%

Section: Androgen Receptor (Ar) Inhibitormentioning

confidence: 99%

Pyridine Moiety: Recent Advances in Cancer Treatment

Sahu¹,

Mishra²,

Kumar³

et al. 2021

ijps

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“…64, No. 2 (2021) treatment of various diseases, including cancer [16,17]. Steroidal heterocycles have drawn great attention due to their interesting structural features as well as their biological profiles [18].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Anti-Proliferative Activity and SAR studies of Novel 5-(3-Indolyl)-5H-Thiazolo[4,3-b][1,3,4]Thiadiazoles tethered with Steroid Moieties

et al. 2020

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A new series of the fused thiazolo[4,3-b]-1,3,4-thiadiazoles 2a-e have been synthesized via one-pot reaction of N-substituted indole-3-carboxaldehydes 1a-e with thioglycolic acid and thiosemicarbazide under grinding condition. Condensation reaction of 2a-e with acetylated epiandrosterone and progesterone afford the corresponding Schiff's bases 3a-e and 4a,b, respectively. Besides, the chloroacetylation of 2a-e in situ by chloroacetyl chloride yielded the chloroacetamides 5a-e. The reaction of 5a-e with 3-amino-pyrazolopyridine derivative 6 provided the goal 2-The analytical and spectral data of the entire target compounds 3a-e, 4a,b and 7a-e were compatible with their structures. Compounds 3a-e, 4a,b, and 7a-e were selected to be screened in vitro against different cancer cell lines, namely A-549, HC-T116, MCF-7, and PC3 using MTT assay. The antiproliferative activity results implied that compounds 3a-e, 4a, and 7e showed excellent growth inhibitory activity toward the human colon cancer cell (HCT-116) with IC50 value ranging from 7.25-38.92 μM/ml in comparison to the reference drug doxorubicin with IC50 of 48.02 μM/ml. Interestingly, compound 3e found to be the most active one towards A-549, HCT-116, and PC3 cancer cell lines with IC50 of 27.05, 12.69, and 24.61µM/ml in comparison with doxorubicin of IC50 39.74, 48.02, and 34.77µM/ml, respectively. In addition, molecular docking studies helped to rationalize the binding interaction of the most active compounds toward human colon cancer cell (HCT-116) 3a-e, 4a and 7a with the anti-apoptotic Bcl-2 and the result revealed that the docking of compounds was more potent compared co-crystalline ligand.

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“…35 Recently, polysubstituted steroidal pyridines were evaluated for cytotoxic potential of prostate cancer cell lines using androgen inhibitor abiraterone as control drug (Figure 1). 36 In continuation of our interests in steroidal β-formyl enamides, 21,23,24 herein, we report the synthesis of a new series of D-ring-fused pyridosteroids, and evaluation of their cytotoxic activities by inducing apoptosis against prostate cancer cells. The novel androst [17,16-b]pyridine and nonsteroidal pyridine derivatives were derived from the reaction of corresponding βformyl enamides 37−39 with alkynes.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis of D-Ring Annulated Pyridosteroids from β-Formyl Enamides and Their Biological Evaluations

et al. 2018

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Herein, we report the synthesis of a novel class of substituted androst[17,16-b]pyridines (pyridosteroids) from the reaction of β-formyl enamides with alkynes in high yields. The optimized reaction protocol was extended to acyclic and cyclic β-formyl enamides to afford nonsteroidal pyridines. Cell survival assay of all compounds were carried against prostate cancer PC-3 cells wherein 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine showed the highest cytotoxic activity. Phase contrast microscopy and flow cytometry studies exhibited marked morphological features characteristic of apoptosis in 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine and abiraterone treated PC-3 cells. The treatment of 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine induces G2/M phase cell cycle arrest in prostate cancer PC-3 cells. Enhancement of apoptotic inductions of PC-3 cells by 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine and abiraterone through the activation of caspases-6, -7, and -8 pathways were supported by qRT-PCR. In silico study of the compound 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine showed stable and promising interaction with the key caspase proteins. Our studies revealed that the pyridosteroid 3-hydroxy-5-en-2′,3′-dicarbethoxy-androst[17,16-b]pyridine, bearing pyridine-2,3-dicarbethoxy pharmacophore, facilitated initiation of caspase-8 and activates downstream effectors caspase-6 and caspase-7 and thereby triggering apoptosis of PC-3 cancer cells.

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Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents

Cited by 38 publications

References 29 publications

Pyridine Moiety: Recent Advances in Cancer Treatment

Pyridine Moiety: Recent Advances in Cancer Treatment

Synthesis, Anti-Proliferative Activity and SAR studies of Novel 5-(3-Indolyl)-5H-Thiazolo[4,3-b][1,3,4]Thiadiazoles tethered with Steroid Moieties

Synthesis of D-Ring Annulated Pyridosteroids from β-Formyl Enamides and Their Biological Evaluations

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