Structure-Based Design of Novel Tetrahydro-Beta-Carboline Derivatives with a Hydrophilic Side Chain as Potential Phosphodiesterase Inhibitors.
| Autor: | Elhady AK; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt. ahmed.elhady@guc.edu.eg., Sigler SC; Department of Oncologic Sciences and Pharmacology, Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36608, USA. sara_sigler@hotmail.com., Noureldin N; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt. nazih.noureldin@guc.edu.eg., Canzoneri JC; Department of Oncologic Sciences and Pharmacology, Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36608, USA. jcanzoneri@adtpharma.com., Ahmed NS; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt. nermin.salah@guc.edu.eg., Piazza GA; Department of Oncologic Sciences and Pharmacology, Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36608, USA. gpiazza@health.southalabama.edu., Abadi AH; Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt. ashraf.abadi@guc.edu.eg. |
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| Jazyk: | angličtina |
| Zdroj: | Scientia pharmaceutica [Sci Pharm] 2015 Sep 26; Vol. 84 (3), pp. 428-446. Date of Electronic Publication: 2015 Sep 26. |
| DOI: | 10.3390/scipharm84030428 |
| Abstrakt: | Tadalafil is a clinically approved phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction and pulmonary arterial hypertension. It contains two chiral carbons, and the marketed isomer is the 6R , 12aR isomer with a methyl substituent on the terminal nitrogen of the piperazinedione ring. In this report, tadalafil analogues with an extended hydrophilic side chain on the piperazine nitrogen were designed to interact with particular hydrophilic residues in the binding pocket. This leads to analogues with moderate inhibitory activity on phosphodiesterase-5, even for isomers in which chiral carbons are of the S configuration. Competing Interests: The authors declare no conflict of interest. |
| Databáze: | MEDLINE |
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