- Research article
- Open Access
Molecular docking and biological evaluation of some thioxoquinazolin-4(3H)-one derivatives as anticancer, antioxidant and anticonvulsant agents
© The Author(s) 2017
- Received: 18 November 2016
- Accepted: 16 May 2017
- Published: 31 May 2017
The quinazoline are an important class of medicinal compounds that possess a number of biological activities like anticancer, anticonvulsant and antioxidant etc.
We evaluated the previously synthesized quinazoline derivatives 1–3 for their anticancer activities against three cancer cell lines (HepG2, MCF-7, and HCT-116). Among the tested compounds, quinazolines 1 and 3 were found to be more potent than the standard drug Vinblastine against HepG2 and MCF-7 cell lines. All the tested compounds had less antioxidant activity and did not exhibit any anticonvulsant activity. Also, molecular docking studies were performed to get an insight into the binding modes of the compounds with human cyclin-dependent kinase 2, butyrylcholinesterase enzyme, human gamma-aminobutyric acid receptor. These compounds showed better docking properties with the CDK2 as compared to the other two enzymes.
The overall study showed that thioxoquinazolines are suitable antitumor agents and they should be explored for other biological activities. Modification in the available lot of quinazoline and synthesis of its novel derivatives is essential to explore the potential of this class of compounds. The increase in the threat and with the emergence of drug resistance, it is important to explore and develop more efficacious drugs.
- Anticancer activity
- Antioxidant activity
- Anticonvulsant activity
- Molecular docking
It is reported that during metabolism and respiration in human body, the free radicals and reactive oxygen species (ROS) are produced that causes a number of devastating effects on human health [41, 42]. Over production of ROS is responsible for oxidative damage to DNA that leads to different kinds of cancers [43, 44]. The oxidative damage by free radicals and ROS is blocked by the antioxidants . Antioxidants act by several ways, scavenging free radicals is one of them. To reduce the effects of oxidation on human body, novel and effective antioxidants are required . Here we intended to study the bioactivities of some thioxoquinazolinone derivatives as anticancer, antioxidant and anticonvulsant agents with an aim to find new drugs of synthetic origin. A docking study was performed to fit the proposed quinazolines 1–3 into the active site of human cyclin-dependent kinase 2 enzyme, human butyrylcholinesterase enzyme, and human gamma-aminobutyric acid receptor in order to study the interaction between binding model and their anticancer, antioxidant and anticonvulsant activities.
The antioxidant activity of the compounds was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay . Fresh 0.004% (w/v) methanol solution of DPPH was prepared and stored at 10 °C in the dark. A methanol solution of the test compounds were also made. A 40 μl aliquot of the methanol solution of the test compound was added to 3 ml of DPPH solution. Absorbance measurements were recorded immediately with a Milton Roy Spectronic 201 UV–visible spectrophotometer. The decrease in absorbance at 515 nm was determined continuously, with data being recorded at 1 min intervals until the absorbance stabilized (16 min). Ascorbic acid was used as a reference standard and dissolved in distilled water to make the stock solution with the same concentration. The absorbance of the DPPH radical without antioxidant was also measured as control and 95% methanol was used as blank. All the determinations were performed in three replicates and averaged.
The anticonvulsant activity was measured according to the reported methods [42, 43]. A total number of animals used for the study consisted of 53 Wister Albino Mice, 20 adult Wister Albino Rats, and 20 day-old Chicks. Stimulator, constant current unit, and corneal electrode were used for the evaluation of the anticonvulsant activity. All of the under investigation quinazolines compounds were suspended in 30% aqueous solution of PEG 400 and administered intraperitoneally in a volume of 0.01 mg/kg at body weight to the mice. Control animals received 30% aqueous form of PEG 400. The quinazolines 1−3 were tested for their anticonvulsant activity against MES-induced seizures and the rotorod toxicity test. Rotorod toxicity test was performed on a 1-in. diameter knurled wooden rod; rotating at 6 rpm.
Anticonvulsant effects in the maximal electroshock seizure (MES) test
Maximal electroshock seizures are elicited in mice with a 60-cycle alternating current of 50 mA intensity delivered for 0.2 s via corneal electrodes. A drop of 0.9% saline is introduced in the eye prior to application of the electrodes in order to prevent the death of the animal. Abolition of the hind limb tonic extension component of the seizure indicated protection against the spread of MES-induced seizures.
The data were expressed as mean ± S.D. The statistical significance of the difference between mean values was determined by Student’s unpaired t test. Data were considered statistically significant at a significance level of P < 0.05. The stata statistical analysis package was used for calculation of IC50 from the dose response curve.
Docking studies were performed using the MOE 2014.09 software package. The protein data bank (PDB) files of the crystal structures of human cyclin-dependent kinase 2 having PDB entry number 1PXO , butyrylcholinesterase with PDB ID 4XII and human gamma-aminobutyric acid receptor having PDB ID 4COF were downloaded from the protein data bank website. Regularization and optimization for protein and ligand were performed. Determination of the essential amino acids in binding site were carried out and compared with the present literature. The performance of the docking method was evaluated by redocking the crystal ligands into the assigned active site of the respective enzymes to determine the root mean square deviation (RMSD) values. The interactive docking method was carried out for all the conformers of each compound in the selected active site. Each docked compound was assigned a score according to its fit in the ligand binding pocket (LBP) and its binding mode.
The inhibitory activities of the tested compounds against three tumor cell lines compared with reference standards
3.0 ± 0.4
3.1 ± 0.6
4.4 ± 0.9
9.5 ± 1.2
9.7 ± 1.8
10.6 ± 2.1
3.9 ± 0.6
3.3 ± 0.6
5.7 ± 0.5
4.3 ± 0.7
4.6 ± 0.8
2.4 ± 0.3
0.5 ± 0.1
0.4 ± 0.1
0.4 ± 0.1
The results from Figs. 2, 3, 4 and Table 1 revealed that quinazolines 1 and 3 were more potent than standard drug Vinblastine sulfate against HepG2 and MCF-7 cell lines with IC50 values = 3.0, 3.1, and 3.9, 3.3, respectively. However, all the tested compounds were less potent than doxorubicin
The in vitro antioxidant activity of quinazolines 1–3 in DPPH method
78 ± 4
312 ± 13
124 ± 9
11 ± 2
Quantitative anticonvulsant data for mice using maximal electroshock test
Maximal electroshock ED50 (mg/kg)
10.3 ± 0.6
All dock runs were conducted using MOE 2014.09 software.
The binding mode of the quinazoline derivatives 1–3 with the human cyclin-dependent kinase 2
The molecular docking study of quinazoline 2 into the binding pocket of human cyclin-dependent kinase 2 enzyme revealed two interactions; arene-cation interaction with bond length of 3.78 Å and binding energy of −2.9 (kcal/mol) and hydrogen bond acceptor interaction with bond length of 3.59 Å and binding energy of −1.5 (kcal/mol) with Lys129. It also showed a hydrogen donor interaction with bond length of 3.28 Å and binding energy of −0.8 (kcal/mol) with Asp145, in addition to arene-hydrogen interaction with bond length of 4.64 Å and binding energy of −0.6 (kcal/Mol) with Glu12 (Fig. 5b).
Alignment study of docked quinazoline 3 into the active binding pocket of the human cyclin-dependent kinase 2 enzyme (Fig. 5c) revealed arene-hydrogen interaction with bond length of 4.23 Å and binding energy of −0.6 (kcal/mol) with Ile10. There was a hydrogen acceptor interaction between Gln131 and one of the sulphur atom of the compound with bond length of 4.05 Å and binding energy of −1.1 kcal/mol.
The binding mode of the quinazoline derivatives 1−3 with the human butyrylcholinesterase
The binding mode of the quinazoline derivatives 1–3 with human gamma-aminobutyric acid receptor
Drug-like properties of the quinazolines 1–3
Molecular weight (g/mol)
We tested the three thioxoquinazolines derivative compounds on three different types of cancer cells and they all showed cytotoxicity to them. These thioxoquinazolines were active against the cancer cell lines in different concentrations. The molecular docking studies of the thioxoquinazoline derivatives with the human cyclin dependent kinase showed several interactions and have favorable docking free energies. These docking studies of quinazoline with cyclin dependent kinase 2 are in agreement with other studies [52–54]. Further these analogues also showed favorable interactions inside the active site of human butyrylcholinesterase and gamma-aminobutyric acid receptor. The quinazolines analogues are also working as an antioxidants and they showed IC50 values between 78 μg/ml and 312 μg/ml as compared to the standard ascorbic acid that has a IC50 of 11 μg/ml. Although they are not as much potent antioxidant as ascorbic acid but their antioxidant properties can be increased by attaching suitable substituents with the quinazoline nucleus [55, 56]. Some quinazolines also posses anticonvulsant activities  and that is why we tested our synthesized compound for this purpose but unfortunately we did not observe such properties. Therefore, it is necessary to screen such quinazoline compounds for a number of biological activities.
The results showed that the quinazolinones 1 and 3 were more potent than standard drug Vinblastine sulfate against HepG2 and MCF-7 cell lines, all the tested compounds had low antioxidant activity compared with the reference standard ascorbic acid. In the near future, it will be better to utilized QSAR and virtual screening methods to design and select more suitable quinazoline ligands that posses better anticancer and antioxidant activities. The three tested compounds here showed no anticonvulsant activity. This work on testing thioxoquinazoline for biological activities is an initial effort and these and other synthesized compounds will be tested for antimicrobial, antiviral and antimalarial activities.
DA and MA conceived, designed and performed the experiments; NK, YM and SB analyzed the data and edited the paper. All authors read and approved the final manuscript.
The authors extend their sincere appreciation to the Deanship of Scientific Research at king Saud University for its funding this Prolific Research group (PRG-1437-29). Also, the authors are thankful to Ahmed Abdelshafy Khedr Chemistry department—faculty of science—Cairo University for the molecular docking.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Gawad NMA, Georgey HH, Youssef RM, El-Sayed NA (2010) Synthesis and antitumor activity of some 2, 3-disubstituted quinazolin-4(3H)-ones and 4, 6-disubstituted-1, 2, 3, 4-tetrahydroquinazolin-2H-ones. Eur J Med Chem 45:6058–6067. doi:10.1016/j.ejmech.2010.10.008 View ArticleGoogle Scholar
- He J, Wang X, Zhao X et al (2012) Synthesis and antitumor activity of novel quinazoline derivatives containing thiosemicarbazide moiety. Eur J Med Chem 54:925–930. doi:10.1016/j.ejmech.2012.06.003 View ArticleGoogle Scholar
- Marvania B, Lee PC, Chaniyara R et al (2011) Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates. Bioorg Med Chem 19:1987–1998. doi:10.1016/j.bmc.2011.01.055 View ArticleGoogle Scholar
- Li HQ, Li DD, Lu X et al (2012) Design and synthesis of 4,6-substituted-(diaphenylamino) quinazolines as potent EGFR inhibitors with antitumor activity. Bioorg Med Chem 20:317–323. doi:10.1016/j.bmc.2011.10.085 View ArticleGoogle Scholar
- Ismail RSM, Ismail NSM, Abuserii S, El Ella DAA (2016) Recent advances in 4-aminoquinazoline based scaffold derivatives targeting EGFR kinases as anticancer agents. Future J Pharm Sci 2:9–19. doi:10.1016/j.fjps.2016.02.001 View ArticleGoogle Scholar
- Boyapati S, Kulandaivelu U, Sangu S, Vanga MR (2010) Synthesis, antimicrobial evaluation, and docking studies of novel 4-substituted quinazoline derivatives as DNA-gyrase inhibitors. Arch Pharm (Weinheim) 343:570–576. doi:10.1002/ardp.201000065 View ArticleGoogle Scholar
- Asif M (2014) Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives. Int J Med Chem 2014:1–27. doi:10.1155/2014/395637 Google Scholar
- Xu GF, Song BA, Bhadury PS et al (2007) Synthesis and antifungal activity of novel s-substituted 6-fluoro-4-alkyl(aryl) thioquinazoline derivatives. Bioorg Med Chem 15:3768–3774. doi:10.1016/j.bmc.2007.03.037 View ArticleGoogle Scholar
- Al-deeb AO, Alafeefy AM (2008) Synthesis of some new 3H-quinazolin-4-one derivatives as potential antitubercular agents. Appl Sci 5:94–99Google Scholar
- Í Kune J, Jaroslav B, Pour M et al (2000) Quinazoline derivatives with antitubercular activity. Farmaco 55:725–729. doi:10.1016/S0014-827X(00)00100-2 View ArticleGoogle Scholar
- Kumar KS, Ganguly S, Veerasamy R, De Clercq E (2010) Synthesis, antiviral activity and cytotoxicity evaluation of Schiff bases of some 2-phenyl quinazoline-4(3)H-ones. Eur J Med Chem 45:5474–5479. doi:10.1016/j.ejmech.2010.07.058 View ArticleGoogle Scholar
- Krishnan SK, Ganguly S, Veerasamy R, Jan B (2011) Synthesis, antiviral and cytotoxic investigation of 2-phenyl-3-substituted quinazolin-4(3H)-ones. Eur Rev Med Pharmacol Sci 15:673–681Google Scholar
- Ye C, You J, Li X et al (2010) Design, synthesis and anticoccidial activity of a series of 3-(2-(2-methoxyphenyl)-2-oxoethyl) quinazolinone derivatives. Pestic Biochem Physiol 97:194–198. doi:10.1016/j.pestbp.2010.02.001 View ArticleGoogle Scholar
- You J, Ye C, Weng Y et al (2008) Synthesis and anticoccidial activity of 4-(2-methoxyphenyl)-2-oxobutylquinazolinone derivatives. Arkivoc 2008:1–11Google Scholar
- Alafeefy AM, Kadi AA, Al-Deeb OA et al (2010) Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline derivatives. Eur J Med Chem 45:4947–4952. doi:10.1016/j.ejmech.2010.07.067 View ArticleGoogle Scholar
- Giri RS, Thaker HM, Giordano T et al (2009) Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-kappaB and AP-1 mediated transcription activation and as potential anti-inflammatory agents. Eur J Med Chem 44:2184–2189. doi:10.1016/j.ejmech.2008.10.031 View ArticleGoogle Scholar
- Alagarsamy V, Solomon VR, Dhanabal K (2007) Synthesis and pharmacological evaluation of some 3-phenyl-2-substituted-3H-quinazolin-4-one as analgesic, anti-inflammatory agents. Bioorg Med Chem 15:235–241. doi:10.1016/j.bmc.2006.09.065 View ArticleGoogle Scholar
- Hemalatha K, Girija K (2011) Synthesis of some novel 2, 3-disubstituted quinazolinone derivatives as analgesic and anti-inflammatory agents. Int J Pharm Pharm Sci 3:6–9Google Scholar
- Kumar A, Sharma S, Archana A et al (2003) Some new 2,3,6-trisubstituted quinazolinones as potent anti-inflammatory, analgesic and COX-II inhibitors. Bioorg Med Chem 11:5293–5299. doi:10.1016/S0968-0896(03)00501-7 View ArticleGoogle Scholar
- Balakumar C, Lamba P, Kishore D Pran et al (2010) Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines. Eur J Med Chem 45:4904–4913. doi:10.1016/j.ejmech.2010.07.063 View ArticleGoogle Scholar
- Mosaad SM, Mohamed KI, Ahmed MA, Sami GA, Adel MM (2005) Synthesis and anti-inflammatory evaluation of some quinazoline derivatives. Int J Pharm 1:261–266View ArticleGoogle Scholar
- Jatav V, Mishra P, Kashaw S, Stables JP (2008) Synthesis and CNS depressant activity of some novel 3- [5-substituted 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. Eur J Med Chem 43:135–141. doi:10.1016/j.ejmech.2007.02.004 View ArticleGoogle Scholar
- Kashaw SK, Kashaw V, Mishra P et al (2009) Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea. Eur J Med Chem 44:4335–4343. doi:10.1016/j.ejmech.2009.05.008 View ArticleGoogle Scholar
- Jatav V, Mishra P, Kashaw S, Stables JP (2008) CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4(3H)-ones. Eur J Med Chem 43:1945–1954. doi:10.1016/j.ejmech.2007.12.003 View ArticleGoogle Scholar
- Werbel LM, Degnan M (1987) Synthesis and antimalarial and antitumor effects of 2-amino-4-(hydrazino and hydroxyamino)-6-[(aryl)thio] quinazolines. J Med Chem 30:2151–2154View ArticleGoogle Scholar
- Kabri Y, Azas N, Dumètre A et al (2010) Original quinazoline derivatives displaying antiplasmodial properties. Eur J Med Chem 45:616–622. doi:10.1016/j.ejmech.2009.11.005 View ArticleGoogle Scholar
- Selvam TP, Kumar PV, Kumar AS (2010) Synthesis and anti-oxidant activity of novel 6,7,8,9 tetra hydro-5H-5-(2′-hydroxy phenyl)-2-(4′-substituted benzylidine)-3-(4-nitrophenyl amino) thiazolo quinazoline derivatives. Res Biotechnol 1:38–48Google Scholar
- Agarwal KC, Sharma V, Shakya N, Gupta S (2009) Design and synthesis of novel substituted quinazoline derivatives as antileishmanial agents. Bioorg Med Chem Lett 19:5474–5477. doi:10.1016/j.bmcl.2009.07.081 View ArticleGoogle Scholar
- Kim YH, Choi H, Lee J et al (2008) Quinazolines as potent and highly selective PDE5 inhibitors as potential therapeutics for male erectile dysfunction. Bioorg Med Chem Lett 18:6279–6282. doi:10.1016/j.bmcl.2008.09.108 View ArticleGoogle Scholar
- Sasmal S, Balasubrahmanyam D, Reddy HRK et al (2012) Design and optimization of quinazoline derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: part 2. Bioorg Med Chem Lett 22:3163–3167. doi:10.1016/j.bmcl.2012.03.049 View ArticleGoogle Scholar
- AL-ALshaikh M, AL-Shammary D, EL-Baih F (2013) Synthesis of some-2-thioxo-3-substituted-2,3-dihydro-1H-quinazolin-4-one derivatives as potential antibacterial and antifungal agents. Res J Chem Environ 17:48–52Google Scholar
- Al-Shamary DS, Al-Othman ZA, AL-ALshaikh M (2013) Synthesis of thioxoquinazolin-4(3H)-one derivatives under microwave and ultrasonic irradiation with classical heating. Asian J Chem 25:6569–6574Google Scholar
- Hay RJ, Cleland MM, Durkin S, Reid YA (2000) Cell line preservation and authentication. In: Masters JRW (ed) Animal cell culture: a practical approach. Oxford University Press, New York City, pp 78–80Google Scholar
- Li Z, Liu C, Huang C et al (2016) Quinazoline derivative QPB-15e stabilizes the c-myc promoter G-quadruplex and inhibits tumor growth in vivo. Oncotarget. 7:34266–34276. doi:10.18632/oncotarget.9088 Google Scholar
- Hei Y-Y, Xin M, Zhang H et al (2016) Synthesis and antitumor activity evaluation of 4,6-disubstituted quinazoline derivatives as novel PI3K inhibitors. Bioorg Med Chem Lett 26:4408–4413. doi:10.1016/j.bmcl.2016.08.015 View ArticleGoogle Scholar
- Zhang Y, Yang C-R, Tang X et al (2016) Synthesis and antitumor activity evaluation of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at C4-position. Bioorg Med Chem Lett 26:4666–4670. doi:10.1016/j.bmcl.2016.08.060 View ArticleGoogle Scholar
- Tarozzi A, Marchetti C, Nicolini B et al (2016) Combined inhibition of the EGFR/AKT pathways by a novel conjugate of quinazoline with isothiocyanate. Eur J Med Chem 117:283–291. doi:10.1016/j.ejmech.2016.04.002 View ArticleGoogle Scholar
- Raffa D, Edler MC, Daidone G et al (2004) Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones. Eur J Med Chem 39:299–304. doi:10.1016/j.ejmech.2003.12.009 View ArticleGoogle Scholar
- Qin X, Lv Y, Liu P et al (2016) Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors. Bioorg Med Chem Lett 26:1571–1575. doi:10.1016/j.bmcl.2016.02.009 View ArticleGoogle Scholar
- Wilson AP (2000) Cytotoxicity and viability assays. In: Masters JRW (ed) Animal cell culture: a practical approach. Oxford University Press, New York City, pp 175–219Google Scholar
- Saintigny Y, Makienko K, Swanson C et al (2002) Homologous recombination resolution defect in Werner syndrome. Mol Cell Biol 22:6971–6978. doi:10.1128/MCB.22.20.6971-6978.2002 View ArticleGoogle Scholar
- Krall RL, Penry JK, White BG et al (1978) Antiepileptic drug development: II. Anticonvulsant drug screening. Epilepsia 19:409–428. doi:10.1111/j.1528-1157.1978.tb04507.x View ArticleGoogle Scholar
- Vasconcelos SMM, Lima NM, Sales GTM et al (2007) Anticonvulsant activity of hydroalcoholic extracts from Erythrina velutina and Erythrina mulungu. J Ethnopharmacol 110:271–274. doi:10.1016/j.jep.2006.09.023 View ArticleGoogle Scholar
- Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. Cancer J Clin 61:69–90. doi:10.3322/caac.20107 View ArticleGoogle Scholar
- Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917. doi:10.1002/ijc.25516 View ArticleGoogle Scholar
- Wang S, Meades C, Wood G et al (2004) 2-Anilino-4-(thiazol-5-yl) pyrimidine CDK inhibitors: synthesis, SAR analysis, X-ray crystallography, and biological activity. J Med Chem 47:1662–1675. doi:10.1021/jm0309957 View ArticleGoogle Scholar
- Tabor E (2001) Hepatocellular carcinoma: global epidemiology. Dig liver Dis 33:115–117. doi:10.1016/S1590-8658(01)80062-1 View ArticleGoogle Scholar
- Yen G, Duh P (1994) scavenging effect of methanolic extracts of peanut hulls on free-radical and active-oxygen species. J Agric Food Chem 42:629–632. doi:10.1021/jf00039a005 View ArticleGoogle Scholar
- Ghose AK, Viswanadhan VN, Wendoloski JJ (1998) Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods: an analysis of ALOGP and CLOGP methods. J Phys Chem A 102:3762–3772. doi:10.1021/jp980230o View ArticleGoogle Scholar
- Gibson AE, Arris CE, Bentley J et al (2002) Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O6-substituted guanine derivatives. J Med Chem 45:3381–3393. doi:10.1021/jm020056z View ArticleGoogle Scholar
- Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 64:4–17. doi:10.1016/j.addr.2012.09.019 View ArticleGoogle Scholar
- Taylor P, Wang J, Chen Y et al (2011) De novo design of quinazoline derivatives as CDK2 inhibitors: 3D-QSAR, molecular fragment replacement and Volsurf predictions. Mol Simul. 37:824–836. doi:10.1080/08927022.2011.563302 View ArticleGoogle Scholar
- Vadivelan S, Sinha BN, Irudayam SJ, Jagarlapudi SARP (2007) Virtual screening studies to design potent CDK2-cyclin a inhibitors. J Chem Inf Model 47:1526–1535. doi:10.1021/ci7000742 View ArticleGoogle Scholar
- Lan P, Chen WN, Xiao GK et al (2010) 3D-QSAR and docking studies on pyrazolo[4,3-h] qinazoline-3-carboxamides as cyclin-dependent kinase 2 (CDK2) inhibitors. Bioorg Med Chem Lett 20:6764–6772. doi:10.1016/j.bmcl.2010.08.131 View ArticleGoogle Scholar
- Al-Amiery AA, Kadhum AAH, Shamel M et al (2013) Antioxidant and antimicrobial activities of novel quinazolinones. Med Chem Res 23:236–242. doi:10.1007/s00044-013-0625-1 View ArticleGoogle Scholar
- Hussein MA (2013) Synthesis, anti-inflammatory, and structure antioxidant activity relationship of novel 4-quinazoline. Med Chem Res 22:4641–4653. doi:10.1007/s00044-013-0468-9 View ArticleGoogle Scholar
- Bhandar SV, Deshmane BJ, Dangare SC, Gore ST, Raparti VT, Khachane CV, Sarkate AP (2008) Anticovulsant activities of some novel 3-[5-substituted, 3, 4-thiadiazole-yl]-2-styryl quinazoline-4(3h)-ones. Pharmacologyonline 2:604–613Google Scholar