852239-39-5Relevant academic research and scientific papers
Investigation of some benzoquinazoline and quinazoline derivatives as novel inhibitors of HCV-NS3/4A protease: Biological, molecular docking and QSAR studies
Abuelizz, Hatem A.,Marzouk, Mohamed,Bakheit, Ahmed H.,Al-Salahi, Rashad
, p. 35820 - 35830 (2020)
Morbidity and mortality due to hepatitis C virus (HCV) is a globe health concern. Hence, there is a persistent demand to design and optimize current HCV therapy and develop novel agents. HCV NS3/A4 protease plays an essential role in HCV life cycle and replication. Thus, HCV NS3/A4 protease inhibitors are one of the best therapeutic targets for the identification of novel candidate drugs. Recent studies have shown some benzoquinazolines as potent antiviral agents and promising HAV-3C protease inhibitors. In the present study, a series of benzo[g]quinazolines (1-13) and their quinazoline analogues (14-17) were evaluated for their HCV-NS3/4A inhibitory activities using in vitro assay. Our results revealed that the target compounds inhibited the activity of the NS3/4A enzyme, (IC50 = 6.41 ± 0.12 to 78.80 ± 1.70 μM) in comparison to telaprevir (IC50 = 1.72 ± 0.03 μM) as a reference drug. Compounds 1, 2, 3, 9, 10 and 13 showed the highest activity (IC50 = 11.02 ± 0.25, 6.41 ± 0.12, 9.35 ± 0.19, 9.08 ± 0.20, 16.03 ± 0.34 and 7.21 ± 0.15 μM, respectively). Molecular docking was performed to study the binding modes of the docked-chosen benzo[g]quinazolines, hydrogen bonding, and amino acid residues at the catalytic triad of the NS3/4A enzyme of HCV. The QSAR was determined to explore the relationships between the molecular structures of the targets and their biological activities by developing prediction models among the known HCV NS3/A4 inhibitors and then to predict the inhibitory activity of the target molecules synthesized.
Synthetic approaches, anticancer potential, HSP90 inhibition, multitarget evaluation, molecular modeling and apoptosis mechanistic study of thioquinazolinone skeleton: Promising antibreast cancer agent
El-Messery, Shahenda M.,El-Shafey, Hamed W.,Goda, Fatma E.,Gomaa, Rania M.
, (2020/06/22)
New series of compounds bearing 2-thioquinazolinone scaffold were designed, synthesized as HSP90 inhibitors. Anti-proliferative activity of the synthesized compounds was evaluated against HCT-116, Hela and MCF-7 cell lines and compound 5k was found to be
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, anticancer and apoptosis-inducing activities of quinazoline–isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies
El-Azab, Adel S.,Al-Dhfyan, Abdullah,Abdel-Aziz, Alaa A.-M.,Abou-Zeid, Laila A.,Alkahtani, Hamad M.,Al-Obaid, Abdulrahman M.,Al-Gendy, Manal A.
, p. 935 - 944 (2017/07/24)
A new series of quinazolinone compounds 16–34 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC50: 10.38–38.67 μM and 9.91–15.77 μM, respectively); the comparative IC50 values for 5-fluorouracil and erlotinib in these cells lines were 70.28 μM, 22.24 μM and 15.23 μM, 25.31 μM respectively. The EGFR-TK assay and induction of apoptosis for compound 31 were investigated to assess its potential cytotoxic activity as a representative example of the novel synthesized compounds. At a concentration of 10 μM, compound 31 exhibited efficient inhibitory effect against EGFR-TK and induced apoptosis in MDA-MB-231 cells. Furthermore, a molecular docking study for compound 31 and erlotinib was performed to verify the binding mode toward the EGFR kinase enzyme, and showed a similar interaction as that with erlotinib alone. Graphical Abstract: Compound 31 showed potent antitumor activity and efficient inhibitory effect against EGFR-TK and induced apoptosis of MDA-MB-231 cells at a concentration of 10 μM.
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 (2016/01/15)
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 (2016/09/13)
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
Quinazoline-sulfonamides with potent inhibitory activity against the α-carbonic anhydrase from Vibrio cholerae
Alafeefy, Ahmed M.,Ceruso, Mariangela,Al-Tamimi, Abdul-Malek S.,Del Prete, Sonia,Capasso, Clemente,Supuran, Claudiu T.
, p. 5133 - 5140 (2014/12/10)
Thirteen novel sulfonamide derivatives incorporating the quinazoline scaffold were synthesized by simple, eco-friendly procedures. These compounds were tested for their ability to inhibit the α-carbonic anhydrases (CA, EC 4.2.1.1) from Vibrio cholerae (VchCA) as well as the human α-CA isoforms, hCA I and hCA II. Nine compounds were highly effective, nanomolar inhibitors of the pathogenic enzyme VchCA. Three of them were also highly effective sub-nanomolar inhibitors of the cytosolic isoform II. The best VchCA inhibitor had a KIof 2.7 nM. Many of these developed compounds showed high selectivity for inhibition of the bacterial over the mammalian CA isoforms, with one compound possessing selectivity ratios as high as 97.9 against hCA I and 9.7 against hCA II. Compound 9d was another highly effective VchCA inhibitor presenting a selectivity ratio of 99.1 and 8.1 against hCA I and hCA II, respectively. These results suggest that sulfonamides with quinazoline backbone could be considered suitable tools to better understand the role of bacterial CAs in pathogenesis.
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.
