Design, synthesis, antiproliferative and antibacterial evaluation of quinazolinone derivatives
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A series of novel quinazolinone derivatives bearing a disulfide bond were designed and synthesized. Their in vitro antiproliferative activities were evaluated using CCK-8 assay against SMMC-7721, Hela, A549 and MCF-7 human cancer cell lines and normal cell lines L929. The preliminary bioassay results demonstrated that all compounds 7a–7h, 8a–8h and 9a–9h exhibited antiproliferation with various degrees, and some compounds showed better effects than positive control 5-fluorouracil against different cancer cell lines. Among these compounds, 8c and 9f showed significant antiproliferative activity against SMMC-7721 cells with IC50 values of 2.88 and 2.56 μM, respectively. In Hela cells, compounds 9c and 9d showed highly effective biological activity with IC50 values of 3.16 and 2.68 μM, respectively. Compounds 7a and 9a exhibited good inhibitory effect against A549 cells with IC50 values of 3.53 and 3.54 μM, respectively. In MCF-7 cells, compounds 7e, 8e and 9e displayed excellent activity with IC50 values of 1.26, 1.12 and 1.85 μM, respectively. Besides, most of the tested compounds showed low cytotoxic effect against the normal cell lines L929. Biological evaluation indicated that all the tested compounds possessed antibacterial activity with certain degrees.
KeywordsQuinazolinone Disulfides Antiproliferative and antibacterial activities
We are grateful to the National Natural Science Foundation of China (20971097), the Tianjin Municipal Natural Science Foundation (13JCYBJC24500) and the Training Project of Innovation Team of Colleges and Universities in Tianjin (TD13-5020) for financial support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Abdel-Aziz AA, Abou-Zeid LA, Eldin HK, ElTahir KE, Mohamed MA, El-Enin MA, El-Azab AS (2016) Design, synthesis of 2,3-disubstitued 4(3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents: COX-1/2 inhibitory activities and molecular docking studies. Bioorg Med Chem 24:3818–3828CrossRefGoogle Scholar
- Al-Salem HS, Hegazy GH, El-Taher KE, El-Messery SM, Al-Obaid AM, El-Subbagh HI (2015) Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecar-bothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone. Bioorg Med Chem Lett 25:1490–1499CrossRefGoogle Scholar
- Amir M, Ali I, Hassan MZ (2014) Design, synthesis and anticonvulsant activity of some newer 3H-quinazolin-4-one derivatives. Indian J Chem 53:597–604Google Scholar
- Hroch L, Guest P, Benek O, Soukup O, Janockova J, Dolezal R, Kuca K, Aitken L, Smith TK, Gunn-Moore F, Zala D, Ramsay RR, Musilek K (2017) Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer’s disease treatment. Bioorg Med Chem 25:1143–1152CrossRefGoogle Scholar
- Lakes AL, Carolyn T, Jordan CT, Gupta P, Puleo DA, Hilt JZ, Dziubla TD (2013) Reducible disulfide poly(beta-amino ester) hydrogels for antioxidant delivery. Acta Biomater 68:362–370Google Scholar
- Turos E, Revell KD, Ramaraju P, Gergeres DA, Greenhalgh K, Young A, Sathyanarayan N, Dickey S, Lim D, Alhamadsheh MM, Reynolds K (2008) Unsymmetric aryl-alkyl disulfide growth inhibitors of methicillin-resistant Staphylococcus aureus and Bacillus anthracis. Bioorg Med Chem 16:6501–6508CrossRefGoogle Scholar
- Wang L, Bao BB, Song GQ, Chen C, Zhang XM, Lu W, Wang ZF, Cai Y, Li S, Fu S, Song FH, Yang HT, Wang JG (2017) Discovery of unsymmetrical aromatic disulfides as novel inhibitors of SARS-CoV main protease: chemical synthesis, biological evaluation, molecular docking and 3D-QSAR study. Eur J Med Chem 137:450–461CrossRefGoogle Scholar