Synthesis, pharmacological evaluation and docking studies of progesterone and testosterone derivatives as anticancer agents

Jabeen, Muafia; Choudhry, M. Iqbal; Miana, Ghulam Abbas; Rahman, Khondaker Miraz; Rashid, Umer; Khan, Hizbullah; Arshia,; Sadiq, Abdul

doi:10.1016/j.steroids.2018.05.008

Cited by 22 publications

(14 citation statements)

References 13 publications

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“…Pregnancy is a period characterized by increased levels of circulating female steroidal hormones including estradiol and progesterone, along with profound changes in social, professional, and emotional life (Schiller et al, 2014). Circulating progesterone is elevated during pregnancy and decreases just before the onset of parturition (Jabeen et al, 2018). Circulating progesterone is elevated during pregnancy and decreases just before the onset of parturition (Jabeen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…These hormones have been shown to have an important role in the brain during pregnancy (Numan, 2007). Circulating progesterone is elevated during pregnancy and decreases just before the onset of parturition (Jabeen et al, 2018). There is now convincing evidence that progesterone and related compounds coordinate an indispensable central nervous system activity at physiological concentrations (Turan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Progesterone and fluoxetine treatments of postpartum depressive‐like behavior in rat model

Yang

et al. 2019

Cell Biology International

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Research studies have indicated that alterations in plasma progesterone levels might be associated with the hippocampal synaptic plasticity of postpartum depressive-like behavior. Herein, we assess both progesterone and fluoxetine effects in adult female Sprague-Dawley rats with postpartum depressive-like behavior. Depressive-like behavior of postpartum rats was established using chronic ultra-mild stress (CUMS) method for 1 week from gestation day 15. Postpartum rats that showed depressive-like behavior were treated with either progesterone (subcutaneously, 0.5 mg/kg) from gestation day 17 to gestation day 22 or fluoxetine (by gavage, 10 mg/kg/day) for 4 weeks after birth. Open field and sucrose preference tests were conducted at the start, week 2 and week 4 postpartum. Golgi staining, immunofluorescence and Western blot analyses of rats' hippocampi were conducted on week 4 postpartum. Results showed CUMS increases depressive-like behavior, however, treatment with progesterone and fluoxetine improves this behavior. Both progesterone and fluoxetine treatments increase the numbers of dendritic spines pyramidal neurons in the CA3 region of the hippocampus as well as protein expression levels of microtubuleassociated protein 2 (MAP-2) and synaptophysin (SYP). CUMS-induced decrement of MAP-2 and SYP protein expressions can be prevented by treatment with progesterone in advanced pregnant stage and fluoxetine in the postpartum period.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Progesterone and fluoxetine treatments of postpartum depressive‐like behavior in rat model

Yang

et al. 2019

Cell Biology International

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Figure 3 shows some representative compounds with thiosemicarbazones structure in the clinical trial. In addition, it is reported that combining steroids (progesterone and testosterone) with semicarbazide or thiosemicarbazide moieties could be a good anticancer drug [38]. Inspired by the good biological properties of semicarbazones and thiosemicarbazones, and in continuation with our previous work on the modifications of steroids, we here report the design and synthesis of a series of novel steroidal endoperoxide derivatives with semicarbazone/thiosemicarbazone side-chain ( Figure 4) and their underlying action mechanisms of anticancer activity, wishing to find new effective antitumor agents.…”

Section: Introductionmentioning

confidence: 99%

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Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Wang

et al. 2020

Molecules

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A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

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Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

Acosta-Guzmán

Mahecha-Mahecha

Gamba‐Sánchez

2020

Chemistry A European J

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Herein, we describe a selective late‐stage deoxygenation of sulfoxides based on a novel application of chlorosulfonium salts and demonstrate a new process using these species generated in situ from sulfoxides as the source of electrophilic chlorine. The use of highly nucleophilic 1,3,5‐trimethoxybenzene (TMB) as the reducing agent is described for the first time and applied in the deoxygenation of simple and functionalized sulfoxides. The method is easy to handle, economic, suitable for gram‐scale operations, and readily applied for poly‐functionalized molecules, as demonstrated with more than 45 examples, including commercial medicines and analogues. We also report the results of competition experiments that define the more reactive sulfoxide and we present a mechanistic proposal based on substrate and product observations.

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Synthesis, pharmacological evaluation and docking studies of progesterone and testosterone derivatives as anticancer agents

Cited by 22 publications

References 13 publications

Progesterone and fluoxetine treatments of postpartum depressive‐like behavior in rat model

Progesterone and fluoxetine treatments of postpartum depressive‐like behavior in rat model

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides

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