Assessment of the Antitumor Potentiality of Newly Designed Steroid Derivatives: Pre-Clinical Study

El-kady, Dina S.; Ali, Naglaa A.; Sayed, Alaa H.; Abdelhaliem, Mervat M; Elmegeed, Gamal A.; Ahmed, Hanaa H.

doi:10.31557/apjcp.2019.20.10.3057

Cited by 3 publications

(3 citation statements)

References 67 publications

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“…The new steroidal derivatives were prepared as described in Schemes 1–3. In Scheme 1, acetylated testosterone 1 was prepared in accordance with the reported method (El‐Kady et al, 2019). Pyridinotestosterone 2 derivative was prepared using microwave irradiation for 5 min on the mixture of acetylated testosterone, p ‐methoxy benzaldehyde, malononitrile, and ammonium acetate in absolute ethanol (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

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Microwave‐assisted synthesis of novel steroidal heterocyclic analogs as potent inhibitors of RANKL‐induced osteoclastogenesis

Elmasry

Ali

El-kady

et al. 2023

Drug Development Research

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Osteoporosis is a significant public health issue in our aging population. It is an excessive bone resorption condition brought on by osteoclastogenesis, which makes bones more brittle. In the present work, a series of novel heterosteroidal derivatives have been synthesized using the microwave technique and were evaluated as antiosteoclastogenic agents. The structures of the newly synthesized compounds have been confirmed using analytical and spectral data. The antiosteoclastogenic activity of the newly synthesized compounds was estimated in vitro against osteoclast‐differentiated cells from the RAW 264.7 cell line. The pregnenolone dimer 10, the pyridinotestosterone derivative 2, and the phenylnicotinonitrile pregnenolone derivative 8a attained the most promising antiosteoclastogenic activity displaying IC50 (the half maximal inhibitory concentration) values of 5.45 ± 5.30, 11.88 ± 2.09, and 13.40 ± 3.00 µM, respectively, in comparison with dimethyl itaconate (IC50 = 17.76 ± 3.20 µM) and alendronate (IC50 = 4.48 ± 1.89 µM) as reference compounds. Finally, an in silico ADME (Absorption, Distribution, Metabolism, and Excretion) study was conducted to evaluate the synthesized compounds' pharmacokinetic and drug‐likeness properties. The results manifested that almost all the investigated compounds' properties were compatible with the specified optimal range, which indicates their reassuring pharmacokinetic properties.

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Section: Resultsmentioning

confidence: 99%

“…This compound was obtained as a white powder with a 75% yield; melting point: 90–95°C (El‐Kady et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

Microwave‐assisted synthesis of novel steroidal heterocyclic analogs as potent inhibitors of RANKL‐induced osteoclastogenesis

Elmasry

Ali

El-kady

et al. 2023

Drug Development Research

View full text Add to dashboard Cite

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“…Since most chemotherapeutic agents have undesirable side effects and resistance may also limit therapeutic success, studies have focused on developing anticancer agents with better tolerability and safety profiles [ 12 ]. Using the steroid skeleton for designing new anticancer agents against cervical carcinomas is a promising approach, partly because of the advantages of this structural framework, as well as because these compounds tend to exhibit complex biological activities other than the classical hormonal effects [ 13 , 14 ]. Regarding the design of innovative anticancer molecules, an attractive feature of the steroid backbone is that even minor modifications of the steroid molecule may induce significant changes in the pharmacological profile [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Antineoplastic Effects of 2-(4-Chlorophenyl)-13α-Estrone Sulfamate against the HPV16-Positive Human Invasive Cervical Carcinoma Cell Line SiHa

Ali

Traj

Szebeni

et al. 2023

IJMS

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Cervical carcinoma is one of the most frequent malignant gynecological cancers in women of reproductive age. Because of the poor tolerability of currently available chemotherapeutic agents, efforts have been focused on developing innovative molecules, including steroids, that exert antineoplastic effects with a better safety profile. In addition to their endocrine properties, certain estrogens exhibit additional biological activities, such as antiangiogenic and anticancer effects. Based on previous studies, the antineoplastic properties of 13α-estrone sulfamate derivatives (13AES1-3) were investigated, and the mechanism of action for the most promising compound 13AES3 was explored. Based on their effects on the viability of different human adherent gynecological cancer cells, the SiHa cervical cell line was used for mechanistic experiments. The most active analog 13AES3 was shown to exert considerable proapoptotic effects, as evidenced by a colorimetric caspase-3 assay and fluorescent double staining. It also elicited antimigratory and anti-invasive effects in a concentration-dependent manner, as evidenced by wound healing and Boyden chamber assays, respectively. Regarding their mechanism of action, 13AES derivatives were shown to inhibit tubulin polymerization, and computer simulations provided a possible explanation for the importance of the presence of the chlorophenyl ring on the estrane skeleton. 13AES3 is considered to be the first 13α-estrone derivative with a significant antineoplastic potency against SiHa cancer cells. Therefore, it might serve as a valuable lead molecule for the design of anticancer agents targeting cervical carcinomas.

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Synthesis of steroids containing N’-alkoxydiazene N-oxide groups

et al. 2022

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Assessment of the Antitumor Potentiality of Newly Designed Steroid Derivatives: Pre-Clinical Study

Cited by 3 publications

References 67 publications

Microwave‐assisted synthesis of novel steroidal heterocyclic analogs as potent inhibitors of RANKL‐induced osteoclastogenesis

Microwave‐assisted synthesis of novel steroidal heterocyclic analogs as potent inhibitors of RANKL‐induced osteoclastogenesis

Investigation of the Antineoplastic Effects of 2-(4-Chlorophenyl)-13α-Estrone Sulfamate against the HPV16-Positive Human Invasive Cervical Carcinoma Cell Line SiHa

Synthesis of steroids containing N’-alkoxydiazene N-oxide groups

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