Auspicious role of the steroidal heterocyclic derivatives as a platform for anti-cancer drugs

Tantawy, Mohamed A.; Nafie, Mohamed S.; Elmegeed, Gamal A.; Ali, Ibrahim A. I.

doi:10.1016/j.bioorg.2017.06.006

Cited by 73 publications

(71 citation statements)

References 64 publications

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“…However, noncancerous fibroblasts did not manifest higher sensitivity toward compound 6g, yielding an advantageous feature for this test molecule over cisplatin. 1 The spectrum of L has no characteristic absorption band in the studied wavelength range.…”

Section: Pharmacological Studiesmentioning

confidence: 92%

“…Structural modification of natural sex hormones by the introduction of various heterocyclic moieties may alter the physicochemical properties and the pharmacokinetic behavior, as well as the biological activity of the parent compound [1]. Continuous interest in steroid derivatives with nitrogen-containing heterorings condensed with, or connected to ring D of the sterane framework 2 of 13 arises from the significant pharmacological potential of these molecules [2].…”

Section: Introductionmentioning

confidence: 99%

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Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

et al. 2019

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Taking into account the pharmacological relevance of heterocycle-fused natural steroids, the objective of the current study was to develop a multistep reaction sequence for the efficient synthesis of novel D-ring-condensed 5-amino-1-arylpyrazoles from dehydroepiandrosterone (DHEA). A condensation reaction of 16-formyl-DHEA with hydroxylamine afforded the corresponding oxime, which was demonstrated to be stable in one of its cyclic isoxazoline forms due to possible ring-chain tautomerism. The subsequent base-induced dehydration to a diastereomeric β-ketonitrile, followed by microwave-assisted heterocyclization with different arylhydrazines led to the desired pyrazoles. The generally good yields of the products depended slightly on the electronic character of the substituent present on the aromatic ring of the reagent. The proton dissociation processes of the DHEA-derived heterocycles were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pKa values attributed to the pyrazole NH+ moiety were low (1.8–4.0) and varied by the different substituents of the benzene ring. The antiproliferative effects of the structurally similar compounds were screened in vitro on human cancer cells (namely on HeLa, U2Os, MCF-7, PC-3, and A549), along with a noncancerous cell line (MRC-5). The IC50 values of the most active derivative were determined on all cell lines.

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Section: Pharmacological Studiesmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

et al. 2019

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“…Hybrid anticancer drugs are considered as new therapeutic approach for cancer as they have a potency to overcome most of the pharmacokinetic drawbacks encountered with the use of traditional anticancer medications (Rahman et al, 2007). Therefore, these drugs are gaining approval as a therapeutic option for different forms of cancer (Tantawy et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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

El-kady

Ali

Sayed

et al. 2019

Asian Pac J Cancer Prev

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“…27 The molecular mechanism of the anticancer activity of this group of derivatives is mainly based on the inhibition of the aromatase and sulfatase enzymes. 28 An androstan derivative with a six-membered ring and a five-membered ring (3-pyridinyl; androsta-5,16-dien-3β-ol acetate) is metabolized into products that have enabled fine tuning of a prostate cancer therapy during clinical trials. 29 Recent research pointed at the antiproliferative potential of modified D-homo lactone androstane derivatives synthesized in our laboratory.…”

Section: Introductionmentioning

confidence: 99%

Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells

et al. 2018

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Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d50=138 nm for A-loaded HAp/ChOSL and d50=223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.

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Auspicious role of the steroidal heterocyclic derivatives as a platform for anti-cancer drugs

Cited by 73 publications

References 64 publications

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

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

Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells

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