Synthesis of 16E-[3-methoxy-4-(2-aminoethoxy)benzylidene]androstene derivatives as potent cytotoxic agents

Bansal, Ranju; Guleria, Sheetal

doi:10.1016/j.steroids.2008.07.004

Cited by 30 publications

(28 citation statements)

References 13 publications

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“…In general, it is observed that 16-arylidene group in steroids represents a good pharmacophore for cytotoxic activity. Although introduction of a pyrrolidine group at 3 position of 16-arylidene steroid skeleton again resulted in loss of cytotoxicity as is shown by data of 10 and which is also in agreement with earlier reports from our laboratory, 11) its 17-acetoxy 3-pyrrolidinyl counterpart 11 displayed good cytotoxic effects. It implies that presence of acetoxy group at 17 position is favorable for activity and may lead to maintenance of cytotoxic effects even if unfavorable 3-pyrrolidinyl group is present as is depicted by cytotoxic effects of 11 and also the earlier studies.…”

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confidence: 91%

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Synthesis and Biological Evaluation of 16E-Arylidenosteroids as Cytotoxic and Anti-aromatase Agents

et al. 2011

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Regular ArticleNew targets are being focused by medical chemist with the aim to provide new specific and potent drugs for the treatment of cancer. Mammary tumors represent the most widespread type of malignant neoplasm and most common cause of cancer in women between the ages of 30-54 1) and is the second leading cause of cancer deaths in women today (after lung cancer). About half of these malignancies require a source of estrogens for their growth and development. Estrogens are biosynthesized from androgens by the microsomal cytochrome P-450 enzyme system termed aromatase.2,3) Inhibition of aromatase is an important approach to reducing growth stimulatory effects of estrogens in estrogen-dependent breast cancer. 4) Effective aromatase inhibitors have been developed as therapeutic agents for controlling estrogen-dependent breast cancer. Aromatase inhibitors (AIs) can reduce estrogen production by more than 90% and in addition AIs lack estrogen-agonist activity unlike tamoxifen, the most widely used antiestrogen for the management of breast cancer.5) Recent clinical data have also shown that these inhibitors have greater efficacy than tamoxifen in late-stage disease and preliminary data indicate that this efficacy extends to early disease. Aromatase inhibitors therefore almost certainly replace tamoxifen as the hormonal agents of choice for the treatment of breast cancer. 5,6) Despite the success of the third-generation steroidal and nonsteroidal AIs, they still have some major side effects, such as the increase of bone loss. For this reason, it is important to search for other potent and specific molecules with lower side effects. Taking into consideration the significance of azole groupings of many specific and potent P450 inhibitors including aromatase, 7) we have introduced imidazole group in androstane nucleus in the present study.A large number of potent steroidal derivatives with substitution at position 16 have been described in the literature as potent cytotoxic agents.8-10) Recent work from our laboratory has also demonstrated the effectiveness of 16E-arylidenosteroids as potential antitumour agents.11-13) These observations prompted us to prepare and study some more new 16E-arylidenosteroids possessing an imidazole group to obtain dual cytotoxic as well as aromatase inhibitory effects. Results and DiscussionThe synthetic routes to the preparation of various new steroidal derivatives have been outlined in Charts 1-3. Base catalyzed aldol condensation of dehydroepiandrosterone (DHA) with 4-(3-chloropropoxy)-3-methoxybenzaldehyde Sector-14, Panjab University; Chandigarh-160014, India: and b Pharmaceutical and Medicinal Chemistry, Saarland University; D-66041, Saarbrücken, Germany. Received September 2, 2010; accepted December 27, 2010; published online January 5, 2011 Taking into consideration the structural requirements for cytotoxicity and aromatase inhibition, several new 16E-arylidenosteroidal derivatives have been prepared and evaluated for their cytotoxic and aromatase inhibitory activity. Th...

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confidence: 91%

“…[8][9][10] Recent work from our laboratory has also demonstrated the effectiveness of 16E-arylidenosteroids as potential antitumour agents. [11][12][13] These observations prompted us to prepare and study some more new 16E-arylidenosteroids possessing an imidazole group to obtain dual cytotoxic as well as aromatase inhibitory effects.…”

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Synthesis and Biological Evaluation of 16E-Arylidenosteroids as Cytotoxic and Anti-aromatase Agents

et al. 2011

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“…Recent work from our laboratory has also demonstrated the effectiveness of 16E-arylidenosteroids as potential cytotoxic and aromatase inhibitors [13,14]. These observations prompted us to prepare and study some more new 16E-arylidenosteroids as aromatase inhibitors, in which structural features of various nonsteroidal aromatase inhibitors have been incorporated.…”

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Synthesis and aromatase inhibitory activity of some new 16E-arylidenosteroids

Bansal

Thota

Karkra

et al. 2012

Bioorganic Chemistry

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CitationSynthesis and aromatase inhibitory activity of some new 16E-arylidenosteroids. 2012, 45:36-40 ABSTRACTA new series of 16E-arylidene androstene derivatives has been synthesized and evaluated for aromatase inhibitory activity. The impact of various aryl substituents at 16 position of the steroid skeleton on aromatase inhibitory activity has been observed. The 16E-arylidenosteroids 6, 10 and 11 exhibited significant inhibition of the aromatase enzyme.16-(4-Pyridylmethylene)-4-androstene-3,17-dione (6, IC 50 : 5.2 µM) and 16-(benzo-[1,3]dioxol-5-ylmethylene)androsta-1,4-diene-3,17-dione (11, IC 50 : 6.4 µM) were found to be approximately 5 times more potent in comparison to aminoglutethimide.

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“…Recently some interesting 16E-arylidene androstene derivatives (1) have been reported from our laboratory as strong in vitro inhibitors of the growth of many types of human tumor cells [12][13][14]. One of the compounds possessing diethylamino group (2, Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1) reached up to in vivo xenograft testing stage of Developmental Therapeutic Program of NCI, Bethesda, USA after successfully passing the first two stages i.e. 60 cell line assay and in vivo hollow fiber assay [14]. This encouraged us to further explore the structural motif responsible for the anticancer properties of 16-arylidene androstenes.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antileukemic activity of 16E-[4-(2-carboxy)ethoxybenzylidene]-androstene amides

Bansal

Acharya

2012

Steroids

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Synthesis of 16E-[3-methoxy-4-(2-aminoethoxy)benzylidene]androstene derivatives as potent cytotoxic agents

Cited by 30 publications

References 13 publications

Synthesis and Biological Evaluation of 16E-Arylidenosteroids as Cytotoxic and Anti-aromatase Agents

Synthesis and Biological Evaluation of 16E-Arylidenosteroids as Cytotoxic and Anti-aromatase Agents

Synthesis and aromatase inhibitory activity of some new 16E-arylidenosteroids

Synthesis and antileukemic activity of 16E-[4-(2-carboxy)ethoxybenzylidene]-androstene amides

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