Synthesis, X-ray structural analysis, and cytotoxic activity of some new androstane d-homo lactone derivatives

Djurendić, Evgenija A.; Savić, Marina P.; Klisurić, Olivera R.; Sakač, Marija N.; Bogdanović, Gordana; Jakimov, Dimitar; Gaši, Katarina M. Penov

doi:10.1007/s11224-012-9986-1

Cited by 18 publications

(10 citation statements)

References 14 publications

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“…Compounds 1-4 were synthesized as described in our previous work. 5,25 In this paper we report a rapid and simple one-pot procedure 26 which was modified from our previous work 25 for the synthesis of compound 4 from starting compound 1. Treatment of 4 with thionyl chloride (absolute pyridine, 0 uC for 2 h) gave 17-oxa-Dhomoandrost-4-ene-6,16-dion-3b-yl acetate (5).…”

Section: Synthetic Studiesmentioning

confidence: 99%

“…Antiproliferative activity was evaluated in vitro using the SRB assay, 33 following 48 h treatment with test compounds as previously described. 25 Results were compared with the nonselective antiproliferative drug, Doxorubicin, as well as a clinically approved androstane derivative (Formestane) used in the treatment of ER+ breast cancer, and are presented in Table 3 as IC 50 values (mM). All of the newly synthesized compounds were non-toxic to normal MRC-5 cells, whereas the Doxorubicin was highly toxic to these cells, consistent with the severe side effects associated with Doxorubicin chemotherapy.…”

Section: Antiproliferative Activitymentioning

confidence: 99%

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Synthesis, structural analysis and antiproliferative activity of some novel D-homo lactone androstane derivatives

et al. 2013

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An efficient synthesis of several A,B-modified D-homo lactone androstane derivatives is reported. The synthetic scheme shows the transformation of 17-oxa-D-homoandrost-5-en-16-on-3b-yl acetate 1 into the 5a-hydroxy-17-oxa-D-homoandrostane-6,16-dion-3b-yl acetate (4). After the dehydration of 4, the newly synthesized 6-keto-androst-4-ene-3b-yl acetate derivative 5 was oximinated to give the 6-hydroximino derivative 6, which was converted to A,B-condensed isoxazole derivatives 7 and 8. Compound 4 was also converted (via 6(E)-and 6(Z)-hydroximino derivatives 9 and 10) to the B-seco-cyano derivative 11 under a Beckmann fragmentation, while compound 5 was transformed to the 4b,5b-epoxy derivative 12.Structures were confirmed by IR, 1 H NMR, 13 C NMR, and HRMS, and for 7 and 8 by X-ray crystallography.All compounds were tested in vitro on six malignant cell lines (MCF-7, MDA-MB-231, PC-3, HeLa, HT-29, K562) and one non-tumor MRC-5 cell line. Significant antiproliferative activity was observed for specific compounds against prostate (PC-3), cervical (HeLa) and colon (HT-29) cancer cells, while no compounds showed antiproliferative activity to non-cancerous control cells (MRC-5). Interestingly, 1-8 displayed selective antiproliferative activity against estrogen-independent (ER2, MDA-MB-231) breast cancer cells over estrogen-dependent (ER+, MCF-7) breast cancer cells.

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Section: Synthetic Studiesmentioning

confidence: 99%

Section: Antiproliferative Activitymentioning

confidence: 99%

Synthesis, structural analysis and antiproliferative activity of some novel D-homo lactone androstane derivatives

et al. 2013

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“…29 Recent research pointed at the antiproliferative potential of modified D-homo lactone androstane derivatives synthesized in our laboratory. 30,31 HAp/Ch-PLGA particles loaded with an androstane-based cancer inhibitor (17β-hydroxy-17α-picolyl-androst-5-ene-3β-yl-acetate) also showed high anticancer activity towards lung cancer cells with a simultaneously low toxicity towards healthy cells. 32…”

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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“…Steroids, a fundamental class of biological molecules, have been used both directly as drugs and precursors in the treatment of many diseases [1] . In the last few decades, the chemical modification of steroidal compounds has been one of the promising strategies to obtain new drug candidates.…”

Section: Introductionmentioning

confidence: 99%

“…Steroids, a fundamental class of biological molecules, have been used both directly as drugs and precursors in the treatment of many diseases. [1] In the last few decades, the chemical modification of steroidal compounds has been one of the promising strategies to obtain new drug candidates. This is due to the fact that these compounds bring about to be nontoxic, less vulnerable to multi-drug resistance (MDR), and highly bioavailable because of are capable of penetrating the cell wall.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structural Analysis and Antiproliferative Activity of Nitrogen‐Containing Hetero Spirostan Derivatives: Oximes, Heterocyclic Ring‐Fused and Furostanes

Erdagi

Yıldız

2022

ChemistrySelect

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The present study focuses on the synthesis of spirostan derivatives as potential drug candidates for biological applications. Recently, spirostan derivatives containing the hetero‐atom have attracted great scientific attention due to their anti‐cancer, anti‐diabetes, and anti‐inflammatory properties. In this study, nitrogen‐containing novel spirostan derivatives with substituted oxime, nitrile, pyrazole, isoxazole structures in ring‐A and F were designed and synthesized starting from diosgenin. The intermediates and target derivatives’ chemical structures were characterized by FTIR, HRMS, 1HNMR, 13CNMR, elemental analysis, and HPLC techniques. The target compounds were evaluated for their cytotoxicities in two human cancer cell lines (MCF‐7 and A549). The tested compounds exhibited potent anticancer activity against human breast adenocarcinoma (MCF‐7) and lung adenocarcinoma (A549). On the other hand, the toxicity of the tested compounds against human healthy fetal lung fibroblasts (MCR‐5) indicated that compounds were non‐toxic for the human body. The results showed that compounds may be used as a promising agents for anticancer agents with improved efficacy.

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Synthesis, X-ray structural analysis, and cytotoxic activity of some new androstane d-homo lactone derivatives

Cited by 18 publications

References 14 publications

Synthesis, structural analysis and antiproliferative activity of some novel D-homo lactone androstane derivatives

Synthesis, structural analysis and antiproliferative activity of some novel D-homo lactone androstane derivatives

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

Synthesis, Structural Analysis and Antiproliferative Activity of Nitrogen‐Containing Hetero Spirostan Derivatives: Oximes, Heterocyclic Ring‐Fused and Furostanes

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