Synthesis and preliminary in vitro biological evaluation of 7α-testosterone–chlorambucil hybrid designed for the treatment of prostate cancer
The synthesis of 7α-testosterone–chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl este...
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Veröffentlicht in: | European journal of medicinal chemistry 2013-06, Vol.64, p.442-447 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The synthesis of 7α-testosterone–chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7α-allyltestosterone with 35% overall yield. MTT assays showed that the hybrid is selective towards hormone-dependent prostate cancer cell line (LNCaP (AR+)) and shows similar activity than the parent drug, chlorambucil. Thus, the new hybrid shows promising potential for drug targeting of hormone-dependent prostate cancer through its capacity of delivering chlorambucil directly to the site of treatment. This could extend the use of chlorambucil to prostate cancer in the future.
Two efficient syntheses of 7α-testosterone–chlorambucil hybrid (1) are reported. MTT assays showed that the hybrid is selective towards hormone-dependent prostate cancer cell line (LNCaP) and is as active as chlorambucil. [Display omitted]
•First reported synthesis of 7α-testosterone–chlorambucil hybrid 1.•Two efficient syntheses provided 1 from testosterone with 23% and 35% overall yield, respectively.•The hybrid 1 shows selectivity on hormone-dependent prostate cancer cells (LNCaP).•The hybrid 1 is as active as chlorambucil, the reference drug. |
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ISSN: | 0223-5234 1768-3254 |
DOI: | 10.1016/j.ejmech.2013.04.027 |