New series of 4(3H)-quinazolinone derivatives: syntheses and evaluation of antitumor and antiviral activities
- 245 Downloads
New series of 3-(3-trifluoromethylphenyl)-6-iodo-4(3H)-quinazolinone derivatives bearing thiosemicarbazones, pyrazoles, azomethine moieties at C-2 were synthesized. The obtained products were screened for their expected anticancer activity against; human liver cancer cell line (HepG2), breast cancer cell line (MCF-7) and human lung adenocarcinoma epithelial cell line (A549) tumor cell lines. Cytotoxicity of the synthesized compounds showed good IC50 for some products in comparison with the standard drug, doxorubicin. On the other hand, antiviral activity of the synthesized products against H5N1 showed moderate to weak activity compared to Zanamivir reference drug.
Keywords4(3H)-Quinazolinones Thiosemicarbazones Pyrazoles Schiff’s bases Antitumor activity Antiviral activity
We thank Prof. Dr. Mamdouh M. Ali, Biochemistry Department, National Research Centre, Cairo, Egypt on his help to finish the antitumor part. Also, we thank Prof. Dr. Mohamed A. Ali, Virology Laboratory and Water Pollution Department, National Research Center, Cairo, Egypt on his help to finish the antiviral part.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- Abbas SY, El-Bayouki KAM, Basyouni WM (2016) Utilization of isatoic anhydride in the syntheses of various types of quinazoline and quinazolinone derivatives. Synthetic Commun 46(12):993–1035Google Scholar
- Abbas SY, Farag AA, Ammar YA, Atrees AA, Mohamed AF, El-Henawy AA (2013) Synthesis, characterization, and antiviral activity of novel fluorinated isatin derivatives. Monatshefte für Chemie - Chemical Monthly 144(11):1725–1733Google Scholar
- Al-Omary FAM, Abouzeid LA, Nagi MN, Habib EE, Abdel-Aziz AAM, El-Azab AS, Abdel-Hamide SG, Al-Omar MA, Al-Obaid AM, El-Subbagh HI (2010) Non-classical antifolates. Part 2: Synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones. Bioorg Med Chem 18:2849–2863CrossRefPubMedGoogle Scholar
- Al-Rashood ST, Aboldahab IA, Nagi MN, Abouzeid LA, Abdel-Aziz AAM, Abdel-Hamide SG, Youssef KM, Al-Obaid AM, El-Subbagh HI (2006) Synthesis, dihydrofolate reductase inhibition, antitumor testing, and molecular modeling study of some new 4(3H)-quinazolinone analogs. Bioorg Med Chem 14:860481CrossRefGoogle Scholar
- Aly MM, Mohamed YA, El-Bayouki KAM, Basyouni WM, Abbas SY (2010) Synthesis of some new 4(3H)-quinazolinone-2-carboxaldehyde thiosemicarbazones and their metal complexes and a study on their anticonvulsant, analgesic, cytotoxic and antimicrobial activities-Part-1. Eur J Med Chem 45:3365–3373CrossRefPubMedGoogle Scholar
- Ammar YA, Mohamed YA, El-Gaby MSA, Abbas SY (2011) Synthesis of some biologically active 4(3H)-quinazolinones derived from 2,3-pyridine dicarboxylic anhydride. Chem Sci J CSJ 15:1–10Google Scholar
- Bridges AJ, Zhou H, Cody DR, Rewcastle GW, McMichael A, Showalter HD, Fry DW, Kraker AJ, Denny WA (1996) Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure−Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor. J Med Chem 39:267–276CrossRefPubMedGoogle Scholar
- Griffin RJ, Srinivasan S, Bowman K, Calvert AH, Curtin NJ, Newell DR, Pemberton LC, Golding BT (1998) Resistance-Modifying Agents. 5. Synthesis and Biological Properties of Quinazolinone Inhibitors of the DNA Repair Enzyme Poly(ADP-ribose) Polymerase (PARP). J Med Chem 41:5247–5256CrossRefPubMedGoogle Scholar
- Khatab TK, El-Bayouki KAM, Basyouni WM, El-Basyoni FA, Abbas SY, Mostafa EAA (2015) novel series of 2,3-dihydroquinazolin-4(1H)-one derivatives: Efficient one-pot synthesis and evaluation of antitumor and antiviral activity. Res Pharm Bio Chem Sci 6:281–291Google Scholar
- Sharma VM, Prasana P, Adi Seshu KV, Rao CLL, Kumar GS, Narasimhulu CP, Babu PA, Puranik RC, Subramanyam D, Warlu AV, Rajagopal S, Kumar KBS, Ajaykumar R, Rajagopalan R (2002) Novel indolo[2,1-b]quinazoline analogues as cytostatic agents: synthesis, biological evaluation and structure–activity relationship. Bioorg Med Chem Lett 12:2303–2307CrossRefPubMedGoogle Scholar
- Smaill JB, Rewcastle GW, Loo JA, Gries KD, Chan OH, Reyner EL, Lipka E, Showalter HD, Vincent PW, Elliot WL, Denny WA (2000) Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(Phenylamino)quinazoline- and 4-(Phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides Bearing Additional Solubilizing Functions. J Med Chem 43:1380–1397CrossRefPubMedGoogle Scholar
- Wissner A, Berger DM, Boschelli DH, Floyd MB, Greenbertger LM, Tsou H, Upeslacis E, Wang YF, Zhang N (2000) 4-Anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor kinase and their bioisosteric relationship to the 4-Anilino-6,7-dialkoxyquinazoline inhibitors. J Med Chem 43:3244–3256CrossRefPubMedGoogle Scholar