Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2009; 59(8): 415-421
DOI: 10.1055/s-0031-1296417

Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics

Editio Cantor Verlag Aulendorf (Germany)

Synthesis of Novel Tadalafil Analogues and their Evaluation as Phosphodiesterase Inhibitors and Anticancer Agents

Abadi Ashraf H

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt

,

Abouel-Ella Dalal A

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt

,

Ahmed Nermin S

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt

,

Gary Bernard D

¹Division of Drug Discovery, Department of Biochemistry and Molecular Biology, Southern Research Institute, The University of Alabama at Birmingham, Birmingham, AL, USA

,

Thaiparambil Jose T

¹Division of Drug Discovery, Department of Biochemistry and Molecular Biology, Southern Research Institute, The University of Alabama at Birmingham, Birmingham, AL, USA

,

Tinsley Heather N

¹Division of Drug Discovery, Department of Biochemistry and Molecular Biology, Southern Research Institute, The University of Alabama at Birmingham, Birmingham, AL, USA

,

Keeton Adam B

¹Division of Drug Discovery, Department of Biochemistry and Molecular Biology, Southern Research Institute, The University of Alabama at Birmingham, Birmingham, AL, USA

,

Piazza Gary A

¹Division of Drug Discovery, Department of Biochemistry and Molecular Biology, Southern Research Institute, The University of Alabama at Birmingham, Birmingham, AL, USA

› Author Affiliations

Abstract

Two closely related series of novel β-car-boline 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.

Key words

Key words

Antitumor agents - ß-Carboline derivatives, anticancer activity, phosphodiesterase 5 inhibition - CAS 171596-29-5 - Tadalafil

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