Design, Synthesis and In Vitro Antiproliferative Activity of Novel Isatin‐Quinazoline Hybrids. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Fares, Mohamed; Eldehna, Wagdy M.; Abou‐Seri, Sahar M.; Abdel‐Aziz, Hatem A.; Aly, Mohamed H.; Tolba, Mai F.
• Is Part Of: Archiv der Pharmazie. Volume 348:Issue 2(2015:Feb.)
• Page Start: 144
• Page End: 154
• Publication Date: 2015-02
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201400337
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201400337-sec-0001" sec-type="section"> <p>Using a molecular hybridization approach, a new series of isatin‐quinazoline hybrids <bold>15a–o</bold> was designed and synthesized <italic>via</italic> two different synthetic routes. The target compounds <bold>15a–o</bold> were prepared by the reaction of quinazoline hydrazines <bold>12a–e</bold> with indoline‐2, 3‐diones <bold>13a–c</bold> or by treating 4‐chloroquinazoline derivatives <bold>11a–e</bold> with isatin hydrazones <bold>14a–c</bold>. The <italic>in vitro</italic> anticancer activity of the newly synthesized hybrids was evaluated against the liver HepG2, breast MCF‐7 and colon HT‐29 cancer cell lines. A distinctive selective growth inhibitory effect was observed towards the HepG2 cancer cell line. Compounds <bold>15b</bold>, <bold>15g</bold> and <bold>15l</bold> displayed the highest potency, with IC₅₀ values ranging from 1.0 ± 0.2 to 2.4 ± 0.4 μM, and they were able to induce apoptosis in HepG2 cells, as evidenced by enhanced expression of the pro‐apoptotic protein Bax and reduced expression of the anti‐apoptotic protein Bcl‐2, in addition to increased caspase‐3 levels.</p> </sec> </abstract>