30507-21-2Relevant academic research and scientific papers
Novel benzenesulfonate scaffolds with a high anticancer activity and g2/m cell cycle arrest
Malarz, Katarzyna,Mularski, Jacek,Kuczak, Micha?,Mrozek-Wilczkiewicz, Anna,Musiol, Robert
, (2021)
Sulfonates, unlike their derivatives, sulphonamides, have rarely been investigated for their anticancer activity. Unlike the well-known sulphonamides, esters are mainly used as conve-nient intermediates in a synthesis. Here, we present the first in-depth
Synthesis and in vitro Leishmania promastigote growth inhibition efficacy of novel 4(3H)-quinazolinone derivatives
Ralph, Greg L.,Zuma, Nonkululeko H.,Aucamp, Janine,N'Da, David D.
, p. 39 - 58 (2020/10/30)
Molecular hybridization is an increasingly important strategy in rational drug design and development. A series of novel quinazolinone-triazole hybrids have been synthesized and their antileishmanial activity investigated. Derivatives (E)-3-(prop-2-yn-1-yl)-2-styrylquinazolin-4(3H)-one, and (E)-3-{[1-(4-bromobenzyl)-1H-1,2,3-triazol-4-yl]methyl}-2-styrylquinazolin-4(3H)-one were observed to moderately inhibit the growth of promastigotes. An overall lack of significant antileishmanial activity may be attributable to the poor aqueous solubility of the derivatives. Future research endeavors will focus on potential remediation by investigating the anchoring of hydrophilic moieties to the quinazolinone scaffold.
Design, synthesis and molecular modeling studies of 2-styrylquinazoline derivatives as EGFR inhibitors and apoptosis inducers
Amin, Noha H.,Elsaadi, Mohammed T.,Zaki, Shimaa S.,Abdel-Rahman, Hamdy M.
, (2020/10/21)
Herein, we report the synthesis of novel 2-substituted styrylquinazolines conjugated with aniline or sulfonamide moieties, anticipated to act as potent anticancer therapeutic agents through preferential EGFR inhibition. In doing so, all the synthesized compounds were screened for their in vitro anticancer activities (nine subpanels) at the National Cancer Institute (NCI), USA. The resulting two most active anticancer compounds (7b and 8c) were then chemically manipulated to investigate feasible derivatives (12a-e and 15a-d). MTT cytotoxicity, in vitro cell free EGFR and anti-proliferative activity against EGFR/ A549 cell line evaluation for the most active broadly spectrum candidates (7a/b, 8c/e, 12b and 15d) was conducted. Promising results were obtained for the styrylquinazoline-benzenesulfonamide derivative 8c (IC50 = 8.62 μM, 0.190 μM and = 79.25%), if compared to lapatanib (IC50 = 11.98 μM, 0.190 μM, and 79.25%), respectively. Moreover, its apoptotic induction potential was studied through cell cycle analysis, Annexin-V and caspase-3 activation assays. Results showed a clear cell arrest at G2/M phase, a late apoptotic increase (76 folds) and a fruitful caspase-3 expression change (8 folds), compared to the control. Finally, molecular docking studies of compounds 7a/b, 8c/e, 12b and 15d revealed proper fitting into the active site of EGFR with a low binding energy score for compound 8c (?13.19 Kcal/mole), compared to lapatanib (?14.54 Kcal/mole).
A Facile Microwave and SnCl2Synthesis of 2,3-Dihydroquinazolin-4(1 H)-ones
O'brien, Nicholas S.,McCluskey, Adam
, p. 1176 - 1186 (2020/10/06)
An elegantly simple, facile, and robust approach to a scaffold of biological importance, 2,3-dihydroquinazolin-4(1H)-ones, is reported. A catalytic 1 % SnCl2/microwave-mediated approach afforded access to pure material, collected by cooling and filtration after 20-min microwave irradiation at 120°C. A total of 41 analogues were prepared in isolated yields of 17-99 %. This process was highly tolerant of aliphatic, aromatic, heterocyclic, and acyclic aldehydes, but furan, pyrrole, and thiophene aldehyde reactivity correlated with propensity towards electrophilic addition and/or Diels-Alder addition. As a result, thiophene afforded high yields (80 %) whereas pyrrole carboxaldehyde failed to react. With simple cinnamaldehydes, and in the SbCl3-mediated reaction, and with α,β-unsaturated aldehydes the equivalent quinazolin-4(3H)-ones, and not the 2,3-dihydroquinazolin-4(1H)-ones, was favoured.
Discovery and development of extreme selective inhibitors of the ITD and D835Y mutant FLT3 kinases
Baska, Ferenc,Sipos, Anna,?rfi, Zoltán,Nemes, Zoltán,Dobos, Judit,Szántai-Kis, Csaba,Szabó, Eszter,Szénási, Gábor,Dézsi, László,Hamar, Péter,Cserepes, Mihály T.,Tóvári, József,Garamv?lgyi, Rita,Krekó, Marcell,?rfi, László
supporting information, (2019/10/16)
Aberrant activation of FMS-like tyrosine receptor kinase 3 (FLT3) is implicated in the pathogenesis of acute myeloid leukemia (AML) in 20–30% of patients. In this study we identified a highly selective (phenylethenyl)quinazoline compound family as novel potent inhibitors of the FLT3-ITD and FLT3-D835Y kinases. Their prominent effects were confirmed by biochemical and cellular proliferation assays followed by mice xenograft studies. Our modelling experiments and the chemical structures of the compounds predict the possibility of covalent inhibition. The most effective compounds triggered apoptosis in FLT3-ITD AML cells but had either weak or no effect in FLT3-independent leukemic and non-leukemic cell lines. Our results strongly suggest that our compounds may become therapeutics in relapsing and refractory AML disease harboring various ITD and tyrosine kinase domain mutations, by their ability to overcome drug resistance.
The p53 stabilizing agent CP-31398 and multi-kinase inhibitors. Designing, synthesizing and screening of styrylquinazoline series
Mularski, Jacek,Malarz, Katarzyna,Pacholczyk, Marcin,Musiol, Robert
, p. 610 - 625 (2019/01/04)
Quinazoline derivatives constitute a large family of small-molecule inhibitors of tyrosine kinases. In the current study, the p53 protein reactivator CP-31398 was tested against a panel of kinases on the assumption that it was structurally similar to othe
Convenient synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones: Applications towards the synthesis of drugs
Kumar, Dinesh,Jadhavar, Pradeep S.,Nautiyal, Manesh,Sharma, Himanshu,Meena, Prahlad K.,Adane, Legesse,Pancholia, Sahaj,Chakraborti, Asit K.
, p. 30819 - 30825 (2015/04/22)
Simple, convenient, and green synthetic protocols have been developed for the one pot synthesis of 2,3-disubstituted quinazolin-4(3H)-ones and 2-styryl-3-substituted quinazolin-4(3H)-ones under catalyst and solvent free conditions. The multicomponent reaction (3-MCR) involving isatoic anhydride, an amine, and orthoester afforded the 2,3-disubstituted quinazolin-4(3H)-ones in excellent yields under classical heating at 120 °C for 5 h or under microwave irradiation at 140°C for 20-30 min. The use of ammonium acetate instead of the amine provides the 2-substituted quinazolin-4(3H)-ones. The reactions are compatible with various substituted isatoic anhydrides, aryl/heteroaryl/alkyl/cycloalkyl amines, and orthoesters. The strategies are extended to the one pot tandem condensation involving isatoic anhydride, an amine, orthoester, and aldehyde to afford highly functionalized (E)-3-aryl/heteroaryl-2-styrylquinazolin/(2-(heteroaryl)vinyl)quinazolin-4(3H)-ones. The applications of the methodologies are demonstrated through the synthesis of various drugs which act on the central nervous system such as methaqualone, mebroqualone, mecloqualone, piriquialone, and diproqualone.
STYRYL QUINAZOLINE DERIVATIVES AS PHARMACEUTICALLY ACTIVE AGENTS
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Page/Page column 9-10; 12, (2015/02/25)
The present invention relates to styryl quinazoline derivatives of the general formula (I) and pharmaceutically acceptable solvates, hydrates, salts, regioisomeric and polymorphic forms thereof as well as pharmaceutical compositions containing at least on
Therapeutic reactivation of mutant p53 protein by quinazoline derivatives
Sutherland, Hamish S.,Hwang, In Young,Marshall, Elaine S.,Lindsay, Brent S.,Denny, William A.,Gilchrist, Catherine,Joseph, Wayne R.,Greenhalgh, Debra,Richardson, Emma,Kestell, Philip,Ding, Angela,Baguley, Bruce C.
, p. 2035 - 2045 (2013/01/15)
Summary: Purpose The human tumour suppressor protein p53 is mutated in nearly half of human tumours and most mutant proteins have single amino acid changes. Several drugs including the quinazoline derivative 1 (CP-31398) have been reported to restore p53
Investigating the anti-proliferative activity of styrylazanaphthalenes and azanaphthalenediones
Mrozek-Wilczkiewicz, Anna,Kalinowski, Danuta S.,Musiol, Robert,Finster, Jacek,Szurko, Agnieszka,Serafin, Katarzyna,Knas, Magdalena,Kamalapuram, Sishir K.,Kovacevic, Zaklina,Jampilek, Josef,Ratuszna, Alicja,Rzeszowska-Wolny, Joanna,Richardson, Des R.,Polanski, Jaroslaw
experimental part, p. 2664 - 2671 (2010/06/14)
A group of styrylazanaphthalenes and azanaphthalenediones were synthesized and tested for their anti-proliferative activity. Most of the compounds were obtained with the use of microwave-assisted synthesis. The lipophilicity of the compounds was measured by RP-HPLC and their anti-proliferative activity was assayed against the human SK-N-MC neuroepithelioma and HCT116 human colon carcinoma cell lines. Active compounds were also tested in clonogenity and comet assays. Several quinazolinone and styrylquinazoline analogues were found to have markedly greater anti-proliferative activity than desferoxamine and cis-platin.
