Quinazoline compounds for antitumor treatment (original) (raw)
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Objective: The present investigation is designed to synthesize some new isomeric series of quinazoline-4-one/4-thione derivatives, depending upon on the pharmacophoric model of in-vivo anticancer activity by modifying the structures retaining the fundamental structural features for the activity and screened for their antitumor properties. Methods: A new series of 7-chloro-3-[substituted (amino/phenyl amino)]-2-phenyl quinazolin-4 (3H)-one/thione derivatives and 1-(7-chloro-4-oxo/-2-phenylquinazoline-3 (4H-yl)) substituted urea derivatives were synthesized. The reaction scheme proceeds through 7-chloro-2-phenyl-4H-benzo [d] [1, 3] oxazin-4-one which is the intermediate one. The structures of the newly synthesized compounds were characterised from infrared (IR), H 1 nuclear magnetic resonance (NMR) and mass spectra (m/z) and elemental analysis. The in-vivo antitumor activity was evaluated by body weight analysis, mean survival time and percentage increase in life span methods in Swiss albino mice bearing Ehrilich ascites carcinoma (EAC). Result: The physico-chemical and spectroscopic data established the synthesis of quinazoline derivatives with a common pharmacophore. The synthesized compounds were evaluated for their antitumor properties. Among the newly quinazoline derivatives screened, six compounds (IIh, IIi, IIj, IIIh, IIIi, IIIj)) have shown significant antitumor activity. Conclusion: The quinazoline derivatives obtained from the present study indicates that the amino group at 3 rd position and urea/thiourea group in phenyl hydrazine ring at 3 rd position of quinzoline skeleton are essential for antitumor activity. Compounds IIh, IIi, IIj, IIIh, IIIi and IIIj were found to be biologically active which may be useful as potential resource for the discovery of anti-tumor compound having common quinazoline pharmacophore with lesser toxic effects. Keywords: 7-chloro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one, quinazoline derivatives, in-vivo anti-tumour activity.
Journal of Enzyme Inhibition and Medicinal Chemistry, 2011
Twenty-two quinazoline derivatives have been synthesised and examined for their anti-tumour activity against three tumour cell lines, namely human breast cancer cell line (MCF-7), human cervical cancer cell line (HeLa) and human hepatoma cell line (HepG2). Twelve of the tested compounds have shown promising anti-tumour activity with an IC 50 range of 5.0-9.7 µg/mL. Regarding the spectrum of activity, five compounds exhibited interesting anti-proliferative properties against the three tested cell lines comparable to the reference drug (dasatinib).
Asian Journal of Pharmaceutical and Clinical Research, 2020
Objective: In this study, a series of novel 2,3-disubstituted quinazolines (4a-4l) were synthesized using standard procedures and elucidated through different spectroscopic techniques. Methods: Obtained compounds were evaluated for their cytotoxicity against human breast cancer (MDA-MB-231) and ovarian cancer (SK-O-V3) cell lines using MTT assay. Docking studies with JAK2 protein were performed to elucidate the possible mechanistic insights into these novel quinazoline derivatives. Results: Moderate-to-good in vitro cytotoxic potentials of the newly synthesized molecules were reported against selected human cancer cell lines. Among the tested molecules, compound 4e showed good cytotoxic activity against MD-AMB-231 (14.2 ± 0.86 μM) and against SK-O-V3 (17.7 ± 0.62 µM). Conclusion: The in vitro studies of the newly synthesized quinazoline derivatives reported considerable cytotoxic potentials against both breast and ovarian cancer cell lines and SAR studies suggest that quinazoline derivatives with heterocyclic benzothiazole nucleus with hydrophilic acetamide linkage at the 3 rd position could probably increase the cytotoxic potentials and the presence of chlorine substitution could add more benefit. With the reported bioactivities of these derivatives, further studies on the derivatization could elucidate the broader cytotoxic potentials.
In vivo anti-tumour activity of novel Quinazoline derivatives
European review for medical and pharmacological sciences, 2012
The two scaffold Quinazoline analogues (Compound 21, NSC: 95112/753439 and Compound 12, NSC: D-104834/ 758270) in three different concentrations were evaluated for their anti-tumor activity against Ehrlich ascites carcinoma (EAC) and two different concentration were evaluated for their anti-tumor activity against Dalton's ascites lymphoma (DLA) bearing Swiss albino mice. The in vivo anti-tumor potency of Quinazoline bases was assessed in EAC model by measuring the increase in mean survival time of the drug treated over untreated control mice and treated standard (Gefitinib) mice. Their toxicity was assessed in vivo in normal, standard, and EAC-bearing mice by measuring the drug-induced changes in haematological parameters. The in vivo anti-tumor potency of Quinazoline bases was assessed in DLA model by measuring solid tumor volume, solid tumor weight and % inhibition of the tumor weight of the drug treated over untreated control mice and treated standard (Gefitinib) mice. Among ...
Synthesis of Some Novel Quinazoline Derivatives Having Anti-Cancer Activity
Global journal of pharmacy & pharmaceutical sciences, 2017
General procedures Synthesis of 2-aryl-3-amino-4(3H) quinazolinone from anthranilic acid: Anthranilic acid (0.1mol, 13.71gm) was dissolved in 30ml of dry pyridine by stirring slowly at room temperature. The solution was cooled to 0 °C and a solution of an aromatic acid chloride (4-Chlorobenzoyl chloride) (0.02mole) in 30ml of dry pyridine was added slowly with constant stirring [4,5]. After this addition the reaction mixture was further stirred for half an hour at room temperature and set aside for 1h.
Current perspectives on quinazolines with potent biological activities: A review
Synthetic Communications, 2018
Quinazoline is a heterocyclic compound having biological activities. It is aromatic in nature having bicyclic structure containing benzene ring and pyrimidine ring. Quinazoline and its derivatives are found to have wide range of biological activities that is anticancer, analgesic, antimicrobial, antihypertensive, anticonvulsant, antimalarial, antitumor, and anti-tubercular activities. The purpose of this review is to highlight the recent researches made by researchers on various biological activities of quinazoline derivatives on different targets.
Quinazoline derivatives as potential anticancer agents: a patent review (2007 – 2010)
Expert Opinion on Therapeutic Patents, 2012
Introduction: Due to the increase in knowledge about cancer pathways, there is a growing interest in finding novel potential drugs. Quinazoline is one of the most widespread scaffolds amongst bioactive compounds. A number of patents and papers appear in the literature regarding the discovery and development of novel promising quinazoline compounds for cancer chemotherapy. Although there is a progressive decrease in the number of patents filed, there is an increasing number of biochemical targets for quinazoline compounds. Areas covered: This paper provides a comprehensive review of the quinazolines patented in 2007 --2010 as potential anticancer agents. Information from articles published in international peer-reviewed journals was also included, to give a more exhaustive overview. Expert opinion: From about 1995 to 2006, the anticancer quinazolines panorama has been dominated by the 4-anilinoquinazolines as tyrosine kinase inhibitors. The extensive researches conducted in this period could have caused the progressive reduction in the ability to file novel patents as shown in the 2007 --2010 period. However, the growing knowledge of cancer-related pathways has recently highlighted some novel potential targets for therapy, with quinazolines receiving increasing attention. This is well demonstrated by the number of different targets of the patents considered in this review. The structural heterogeneity in the patented compounds makes it difficult to derive general pharmacophores and make comparisons among claimed compounds. On the other hand, the identification of multi-target compounds seems a reliable goal. Thus, it is reasonable that quinazoline compounds will be studied and developed for multi-target therapies.
European Journal of Medicinal Chemistry, 2010
Novel derivatives of quinazoline (1e27) have been synthesized and tested for their antitumor activity against three tumor cell lines among these cell lines the human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. All tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC 50 range of 3.35e6.81 mg/ml. With regarding broad-spectrum activity compounds 5, 9, 15, 18 and 20 exploited potent antitumor against human liver cell line (HEPG2), human breast cell line (MCF-7) and human cervix cell line (HELA) with IC 50 range of 3.35e5.59 mg/ml. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors.
An acetylhydrazide derivative containing a quinazoline nucleus has been utilized to design and synthesize a series of 2,4-disubstituted quinazolines via reaction with several carbon electrophiles including 4-methoxybenzaldehyde and carbon disulfide as well as acetyl and benzoyl chloride. Another series of 2,3-disubstituted-4(3H)-quinazolinones has been also obtained from reactions of a 3-aminoquinazolin-4(3H)-one derivative with other carbon electrophiles, such as chloroacetamide, acetic anhydride, phenyl isocyanate, and ethyl chloroacetate. The structures of the new compounds have been assigned from their spectral data (IR, 1 H NMR, 13 C NMR and MS) and elemental analyses. The newly synthesized compounds were evaluated for their in vitro cytotoxic activity against breast cancer, hepatocellular carcinoma, cervical cancer, and human promyelocytic leukemia cell lines. All the tested compounds showed anticancer activity.
Tropical Journal of Pharmaceutical Research
Purpose: To evaluate newly synthesized fuoryl quinazoline derivatives for antitumor efficacy.Methods: Fuoryl quinazoline derivatives were synthesized and the structures of the synthesized compounds were characterized using standard techniques. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) technique was used to assess the anti-proliferative properties of the synthesized derivatives in vitro.Results: All quinazoline compounds displayed cytotoxic activity against breast and colon cancer cell lines to varying degrees. Compound IXa with acetohydrazide moiety was the most effective on MCF7 and HCT116 cell lines, with half-maximal inhibitory concentration (IC50) values of 16.70 and 12.54 μM, respectively.Conclusion: N'-benzylidene-2-((2-(furan-2-yl) quinazolin-4-yl) oxy) acetohydrazide IXa showed the strongest anti-proliferative activity against MCF-7 and HCT116 human cancer cell lines.