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. 2009;59(8):415-21.
doi: 10.1055/s-0031-1296417.

Synthesis of novel tadalafil analogues and their evaluation as phosphodiesterase inhibitors and anticancer agents

Ashraf H Abadi  1 , Dalal A Abouel-Ella, Nermin S Ahmed, Bernard D Gary, Jose T Thaiparambil, Heather N Tinsley, Adam B Keeton, Gary A Piazza
Affiliations

Synthesis of novel tadalafil analogues and their evaluation as phosphodiesterase inhibitors and anticancer agents

Ashraf H Abadi et al. Arzneimittelforschung. 2009.

Abstract

Two closely related series of novel beta-carboline derivatives, electronically similar to tadalafil (CAS 171596-29-5), were synthesized and evaluated for their inhibitory effects upon phosphodiesterase 5 (PDE5) and phosphodiesterase 11 (PDE11) and their in vitro tumor cell growth inhibitory activity versus HT29 colorectal carcinoma cell line. Interestingly, some of the synthesized compounds showed growth inhibitory properties that appear to be associated with their ability to inhibit PDE5. Moreover, the PDE5 inhibition seems relevant to the stereochemical aspects of the compounds.

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Figures

Fig. 1
Fig. 1
Torsional angle of the pendant aryl relative to the tetracyclic part for tadalafil (left) and compound V (right).
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Formula 1
Formula 1
Chemical structure of the reference compounds: tadalafil (left) and exisulind (right).
Formula 2
Formula 2
(R, R) isomer: IC50 vs HT29 cancer cell line = 2.5 μm, IC50 vs PDE5 = 5.0 μm.
See this image and copyright information in PMC

References

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