23070-25-9Relevant academic research and scientific papers
Synthesis, antitumor activity and molecular docking study of some novel 3-benzyl-4(3H)quinazolinone analogues
Al-Suwaidan, Ibrahim A.,Abdel-Aziz, Alaa A.-M.,Shawer, Taghreed Z.,Ayyad, Rezk R.,Alanazi, Amer M.,El-Morsy, Ahmad M.,Mohamed, Menshawy A.,Abdel-Aziz, Naglaa I.,El-Sayed, Magda A.-A.,El-Azab, Adel S.
, p. 78 - 89 (2016)
A novel series of 3-benzyl-substituted-4(3H)-quinazolinones were designed, synthesized and evaluated for their in vitro antitumor activity. The results of this study demonstrated that 2-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide, 2-(3-benzyl-6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide and 3-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)-propanamide have shown amazing broad spectrum antitumor activity with mean GI50 (10.47, 7.24 and 14.12 μM. respectively), and are nearly 1.5-3.0-fold more potent compared with the positive control 5-FU with mean GI50, 22.60 μM. On the other hand, compounds 6 and 10 yielded selective activities toward CNS, renal and breast cancer cell lines, whereas compound 9 showed selective activities towards leukemia cell lines. Molecular docking methodology was performed for compounds 7 and 8 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib, while compound 11 into ATP binding site of B-RAF kinase inhibited the growth of melanoma cell lines through inhibition of B-RAF kinase, similar to PLX4032.
Synthesis, biological evaluation and molecular modeling study of some new methoxylated 2-benzylthio-quinazoline-4(3H)-ones as nonclassical antifolates
El-Messery, Shahenda M.,Hassan, Ghada S.,Nagi, Mahmoud N.,Habib, El-Sayed E.,Al-Rashood, Sarah T.,El-Subbagh, Hussein I.
, p. 4815 - 4823 (2016)
A new series of 2,3,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 28 and 61 proved to be active DHFR inhibitors with IC500.02 and
Quinazolin-4(3H)-one based potential multiple tyrosine kinase inhibitors with excellent cytotoxicity
Mirgany, Tebyan O.,Abdalla, Ashraf N.,Arifuzzaman, Md,Motiur Rahman,Al-Salem, Huda S.
, p. 2055 - 2067 (2021/09/28)
A series of quinazolin-4(3H)-one derivatives were synthesised and evaluated for their cytotoxicity against human Caucasian breast adenocarcinoma (MCF-7) and human ovarian carcinoma (A2780) cell lines. Cytotoxicity of the most tested compounds was 2- to 30-fold more than the positive control lapatinib (IC50 of 2j = 3.79 ± 0.96; 3j = 0.20 ± 0.02; and lapatinib = 5.9 ± 0.74) against MCF7 cell lines except two compounds (IC50 of 2 b = 15.72 ± 0.07 and 2e = 14.88 ± 0.99). On the other hand, cytotoxicity was 4 ? 87 folds (IC50 of 3a = 3.00 ± 1.20; 3 g = 0.14 ± 0.03) more the positive control lapatinib (IC50 = 12.11 ± 1.03) against A2780 cell lines except compound 2e (IC50 = 16.43 ± 1.80). Among the synthesised quinazolin-4(3H)-one derivatives, potent cytotoxic 2f-j and 3f-j were investigated for molecular mechanism of action. Inhibitory activities of the compounds were tested against multiple tyrosine protein kinases (CDK2, HER2, EGFR and VEGFR2) enzymes. As expected, all the quinazolin-4(3H)-one derivatives were showed comparable inhibitory activity against those kinases tested, especially, compound 2i and 3i showed potent inhibitory activity against CDK2, HER2, EGFR tyrosine kinases. Therefore, molecular docking analysis for quinazolin-4(3H)-one derivatives 2i and 3i were performed, and it was revealed that compounds 2i and 3i act as ATP non-competitive type-II inhibitor against CDK2 kinase enzymes and ATP competitive type-I inhibitor against EGFR kinase enzymes. However, in case of HER2, compounds 2i act as ATP non-competitive type-II inhibitor and 3i act as ATP competitive type-I inhibitor. Docking results of known inhibitors were compared with synthesised compounds and found synthesised 2i and 3i are superior than the known inhibitors in case of interactions. In addition, in silico drug likeness properties of quinazolin-4(3H)-one derivatives showed better predicted ADME values than lapatinib.
Synthesis of benzensulfonamides linked to quinazoline scaffolds as novel carbonic anhydrase inhibitors
El-Azab, Adel S.,Abdel-Aziz, Alaa A.-M.,Bua, Sivia,Nocentini, Alessio,El-Gendy, Manal A.,Mohamed, Menshawy A.,Shawer, Taghreed Z.,AlSaif, Nawaf A.,Supuran, Claudiu T.
, p. 78 - 90 (2019/03/19)
Carbonic anhydrase (CA) inhibitory activities of newly synthesized quinazoline-linked benzensulfonamides 10–29, 31, 32, 35, 36, and 45–51 against human CA (hCA) isoforms I, II, IX, and XII were measured and compared to that of acetazolamide (AAZ) as a standard inhibitor. Potent selective inhibitory activity against hCA I was exerted by compounds 14, 15, 17, 19, 20, 21, 24, 25, 28, 29, 31, 35, 45, 47, 49, and 51 with inhibition constant (KIs) values of 39.4–354.7 nM that were nearly equivalent or even greater than that of AAZ (KI, 250.0 nM). Compounds 15, 20, 24, 28, 29, 45 and 47 proved to have inhibitory activities against hCA II with (KIs, 0.73–16.5 nM) that were similar or improved to that of AAZ (KI, 12.0 nM). Compounds 13–29, 31–32, and 45–51 displayed potent hCA IX inhibitory activities (KIs, 1.6–32.2 nM) that were more effective than or nearly equal to AAZ (KI, 25.0 nM). Compounds 14, 15, 20, 21, 26, 45, and 47 exerted potent hCA XII inhibitory activities (KIs, 5.2–9.2 nM), indicating similar CAI activities as compared to that of AAZ (KI, 5.7 nM).
Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone
Al-Salem, Huda S.A.,Hegazy, Gehan H.,El-Taher, Kamal E.H.,El-Messery, Shahenda M.,Al-Obaid, Abdulrahman M.,El-Subbagh, Hussein I.
supporting information, p. 1490 - 1499 (2015/03/30)
A new series of quinazoline analogues was designed and synthesized to get the target compounds 18-21, 30-41, 46-53, and 57-76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active, respectively than the used positive control sodium valproate. Structure activity correlation concluded valuable pharmacophoric information which confirmed by molecular modeling studies. Molecular docking study of 68 suggested its agonistic behavior toward GABAA receptor. The studied quinazoline analogues could be considered as useful templates for future development and further derivatization.
Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4-thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors
Al-Rashood, Sarah T.,Hassan, Ghada S.,El-Messery, Shahenda M.,Nagi, Mahmoud N.,Habib, El-Sayed E.,Al-Omary, Fatmah A.M.,El-Subbagh, Hussein I.
, p. 4557 - 4567 (2015/02/19)
A new series of 2-(1,3,4-thiadiazolyl- or 4-methyl-thiazolyl)thio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 29, 34, and 39 proved to be the most active DHFR inhibitors with IC50values range of 0.1-0.6 μM. Compounds 28, 31 and 33 showed remarkable broad-spectrum antimicrobial activity comparable to the known antibiotic Gentamicin. Compounds 26, 33, 39, 43, 44, 50, 55 and 63 showed broad spectrum antitumor activity with GI values range of 10.1-100%. Molecular modeling study concluded that recognition with key amino acid Glu30, Phe31 and Phe34 is essential for binding. ADMET properties prediction of the active compounds suggested that compounds 29 and 34 could be orally absorbed with diminished toxicity.
Nonclassical antifolates, part 3: Synthesis, biological evaluation and molecular modeling study of some new 2-heteroarylthio-quinazolin-4-ones
Al-Omary, Fatmah A.M.,Hassan, Ghada S.,El-Messery, Shahenda M.,Nagi, Mahmoud N.,Habib, El-Sayed E.,El-Subbagh, Hussein I.
, p. 33 - 45 (2013/07/25)
A new series of 2-heteroarylthio-6-substituted-quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 21, 25, and 39 proved to be active DHFR inhibitors with IC50 range of 0.3-0.8 μM. Compounds 25, 28, 33, 35 and 36 showed broad spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compound 29 showed broad spectrum antitumor activity toward several tumor cell lines with GI values range of 25.8-41.2%. Molecular modeling studies concluded that recognition with key amino acid Arg38 and Lys31 are essential for binding and biological activities. Flexible alignment; electrostatic and hydrophobic mappings revealed that the obtained model could be useful for the development of new DHFR inhibitors.
