Novel Quinazolin-4(3H)-one/Schiff Base Hybrids as Antiproliferative and Phosphodiesterase 4 Inhibitors: Design, Synthesis, and Docking Studies

被引：15

作者：

Abdel-Rahman, Hamdy M. ^{[1
]}

Abdel-Aziz, Mohamed ^{[2
]}

Canzoneri, Joshua C. ^{[3
]}

Gary, Bernard D. ^{[3
]}

Piazza, Gary A. ^{[3
]}

机构：

[1] Assiut Univ, Fac Pharm, Dept Med Chem, Assiut, Egypt

[2] Menia Univ, Dept Med Chem, Fac Pharm, Al Minya, Egypt

[3] Univ S Alabama, USA Mitchell Canc Inst, Mobile, AL 36688 USA

来源：

ARCHIV DER PHARMAZIE | 2014年 / 347卷 / 09期

关键词：

Antiproliferative; Docking; Hybrids; PDE4B inhibitors; Quinazolin-4(3H)-one; OBSTRUCTIVE PULMONARY-DISEASE; N-ACYLHYDRAZONES; PDE4; INHIBITORS; DERIVATIVES; POTENT; ASTHMA; CELLS; QUINAZOLINONE; ROFLUMILAST; GROWTH;

D O I：

10.1002/ardp.201400083

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of quinazolin-4(3H)-one/Schiff base hybrids was rationally designed and synthesized. The prepared compounds were evaluated for in vitro activity to inhibit phosphodiesterase 4 (PDE4), where several of them showed good-to-moderate activity compared to rolipram. Compound 7 showed potent PDE4 inhibition in this series, with an IC50 of 1.60 mu M. Compounds that showed PDE4 inhibition were further assessed for antiproliferative activity using different human tumor cell lines. Compound 10 exhibited significant antiproliferative activity with IC50 values of 140, 79, and 320nM in breast, lung, and colon tumor cells, respectively. Docking of compound 7 in the active site of PDE4B illustrates its possible binding mode and provides insight for further optimizations of this novel scaffold for inhibiting PDE4.

引用

页码：650 / 657

页数：8

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