22280-87-1Relevant academic research and scientific papers
Design, synthesis, molecular simulation, and biological activities of novel quinazolinone-pyrimidine hybrid derivatives as dipeptidyl peptidase-4 inhibitors and anticancer agents
Emami, Leila,Faghih, Zahra,Sakhteman, Amirhossein,Rezaei, Zahra,Faghih, Zeinab,Salehi, Farnaz,Khabnadideh, Soghra
, p. 19515 - 19531 (2020)
Two novel series of quinazolinone-pyrimidine (series a: 9a-9i) and benzyl-pyrimidine hybrids (series b: 12a-12c) were designed, synthesized and characterized by spectroscopic methods. The dipeptidyl peptidase-4 inhibition potencies of these compounds were assessed through a MAK 203 kit. Compound 9e was found to be the most potent agent with an IC50 value of 34.3 ± 3.3 μM. A kinetic study revealed that it acted as a competitive inhibitor. Molecular modeling of these compounds was in agreement with the in vitro results. Due to the crucial role of dipeptidyl peptidase-4 in cancer therapy, the cytotoxic activities of the compounds were also evaluated against three cancerous cell lines (HT-29, SW1116 and A549). Almost all the compounds displayed better antiproliferative activity on colon cancer cell lines (HT-29 and SW1116) compared to a lung cancer cell line (A549). Compounds 9e and 12c exhibited significant activity toward the HT-29 cell line with an IC50 of 10.67 ± 0.3 μM and 27.9 ± 6.5 μM in comparison to sitagliptin and cisplatin as a positive control, respectively. Among the different cells, the compounds showed the best inhibitory effects on HT-29, which was compatible with the greater expression of the dipeptidyl peptidase-4 marker detected by flow cytometry in this cell line. Further studies on the hit compounds (9e and 12c) through cell cycle and apoptosis assays also showed that these compounds could induce cell death by apoptosis or arrest cells in the G2/M phase. Accordingly, the results imply that 9e is a potent inhibitor of dipeptidyl peptidase-4 with efficient anti-cancer activity and could play a role as a cytotoxic agent in colorectal cancer.
2-(Chloromethyl)-3-phenylquinazolin-4(3H)-ones as potent anticancer agents; cytotoxicity, molecular docking and in silico studies
Emami, Leila,Faghih, Zeinab,Khabnadideh, Soghra,Rezaei, Zahra,Sabet, Razieh,Harigh, Ebrahim,Faghih, Zahra
, p. 1877 - 1889 (2021/02/27)
Abstract: In order to show antiproliferation and cancerous cell growth inhibition of quinazoline derivatives, a series of 2-(chloromethyl)-3-phenylquinazolin-4(3H)-ones (H1–H11) were synthesized. In vitro cytotoxic activities were evaluated against three human cancer cell lines: A549, MCF-7 and SW1116 using colorimetric MTT assay. Comparing their effects together and with cisplatin as a positive control indicated that H3, H5 and H6 exhibited better antitumor activities on A549 cell line with IC50 values less than 10?μM versus 12?μM for cisplatin. In the case of MCF-7 and SW1116 cell lines, almost all compounds displayed better cytotoxic activities than cisplatin. Molecular docking studies were applied on epidermal growth factor receptor (EGFR) as the main target of quinazoline scaffolds in cancer therapy to predict the binding energies, binding modes and orientation of these ligands toward the active site of the receptor. In silico physicochemical parameters and ADMET profiling calculations also were done. All compounds showed lower binding energies than erlotinib, the inhibitor of EGFR. Taken together, our findings showed potential anticancer effect of quinazoline compounds bearing various phenyl ring substitutions. Graphic abstract: [Figure not available: see fulltext.]
Substituted 4-phenylthiazoles: Development of potent and selective A1, A3 and dual A1/A3 adenosine receptor antagonists
Abdelrahman, Aliaa,Yerande, Swapnil G.,Namasivayam, Vigneshwaran,Klapschinski, Tim A.,Alnouri, Mohamad Wessam,El-Tayeb, Ali,Müller, Christa E.
supporting information, (2019/12/24)
Adenosine acts as a powerful signaling molecule via four distinct G protein-coupled receptors, designated A1, A2A, A2B and A3 adenosine receptors (ARs). A2A and A2B ARs are Gs-coupled, while A1 and A3 ARs inhibit cAMP production via Gi proteins. Antagonists for A1 and A3 ARs may be useful for the treatment of (neuro)inflammatory diseases including acute kidney injury and kidney failure, pulmonary diseases, and Alzheimer's disease. In the present study, we optimized the versatile 2-amino-4-phenylthiazole scaffold by introducing substituents at N2 and C5 to obtain A1 and A3 AR antagonists including dual-target compounds. Selective A1 antagonists with (sub)nanomolar potency were produced, e.g. 11 and 13. These compounds showed species differences being significantly more potent at the rat as compared to the human A1 AR, and were characterized as inverse agonists. Several potent and selective A3 AR antagonists, e.g. 7, 8, 17 and 22 (Ki values of 5–9 nM at the human A3 AR) were prepared, which were much less potent at the rat orthologue. Moreover, dual A1/A3 antagonists (10, 18) were developed showing Ki values between 8 and 42 nM. Docking and molecule dynamic simulation studies using the crystal structure of the A1 AR and a homology model of the A3 AR were performed to rationalize the observed structure-activity relationships.
Novel 2,4- thiazolidinediones: Synthesis, in?vitro cytotoxic activity, and mechanistic investigation
Metwally, Kamel,Pratsinis, Harris,Kletsas, Dimitris
, p. 340 - 350 (2017/04/13)
Two thiazolidinedione scaffolds different in the position of the thiazolidinedione ring in the molecule were tested for in?vitro cytotoxic activity in a panel of human cancer cell lines namely, prostate cancer cells PC-3, breast carcinoma cells MDA-MB-231
Quinazolinone-based rhodanine-3-acetic acids as potent aldose reductase inhibitors: Synthesis, functional evaluation and molecular modeling study
El-sayed, Sherihan,Metwally, Kamel,El-Shanawani, Abdalla A.,Abdel-Aziz, Lobna M.,El-Rashedy, Ahmed A.,Soliman, Mahmoud E.S.,Quattrini, Luca,Coviello, Vito,la Motta, Concettina
, p. 4760 - 4764 (2017/09/29)
A series of quinazolinone-based rhodanine-3-acetic acids was synthesized and tested for in vitro aldose reductase inhibitory activity. All the target compounds displayed nanomolar activity against the target enzyme. Compounds 3a, 3b, and 3e exhibited almo
Synthesis and screening of 2-(2-(4-substituted piperazine-1-yl)-5- phenylthiazol-4-yl)-3-aryl quinazolinone derivatives as anticancer agents
Sharma, Ritesh N.,Ravani, Rasik
, p. 2788 - 2794 (2013/07/26)
Synthesis of novel quinazolinone derivatives was performed from the reaction of N-benzoyl substituted piperazine-1-carbothioamide with 2-chloromethyl quinazolinone derivatives and screened for their in vitro cytotoxic activity by MTT assay. The cell lines
Design, synthesis and evaluation of novel 2-thiophen-5-yl-3H-quinazolin-4-one analogues as inhibitors of transcription factors NF-k{cyrillic}B and AP-1 mediated transcriptional activation: Their possible utilization as anti-inflammatory and anti-cancer ag
Giri, Rajan S.,Thaker, Hardik M.,Giordano, Tony,Williams, Jill,Rogers, Donna,Vasu, Kamala K.,Sudarsanam, Vasudevan
experimental part, p. 2796 - 2808 (2010/07/06)
In an attempt to discover novel inhibitors of NF-κB and AP-1 mediated transcriptional activation utilizing the concept of chemical lead based medicinal chemistry and bioisosterism a series of 2-(2,3-disubstituted-thiophen-5-yl)-3H-quinazolin-4-one analogs
Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents
Giri, Rajan S.,Thaker, Hardik M.,Giordano, Tony,Williams, Jill,Rogers, Donna,Sudersanam, Vasudevan,Vasu, Kamala K.
body text, p. 2184 - 2189 (2009/09/30)
A series of 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives were designed and synthesized. Synthesized molecules were further evaluated for their inhibitory activity towards transcription factors NF-κB and AP-1 mediated transcr
Synthesis of novel thioglycoside derivatives containing quinazolinone
Huang, Hui,Gao, Jian-Fang,Cao, Ling-Hua,Wang, Duo-Zhi,Zhang, Jian-Bin,Zhou, Shu-Bao,Zhou, Yu-Qiang
experimental part, p. 419 - 424 (2009/12/06)
Aseries of novel thioglycoside derivatives containing 4(3H)-quinazolinone was designed and synthesized from 2-chloromethyl-quinazolin-4(3H)-ones and 1-thioglycose. Several 2-chloromethyl-quinazolin-4(3H)-ones were synthesized on refluxing with 2-(chloroacetylamino)-benzoic acid and arylamines in acetonitrile. All of the novel compounds were characterized by IR, 1H NMR spectra and elemental analysis. The structures of compounds 7b, 8b and 8c have been determined by X-ray diffraction analysis.
THIAZOLE AND THIOPHENE ANALOGUES, AND THEIR USE IN TREATING AUTOIMMUNE DISEASES AND CANCERS
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Page/Page column 44, (2008/06/13)
Thiazole and thiophene compounds are disclosed having utility in treating inflammatory conditions, immunoinflammatory conditions, autoimmune diseases, and cancers. Methods for the synthesis of these compounds are also disclosed.
