A Review on the Synthesis and Chemical Transformation of Quinazoline 3-Oxides

Abstract

The synthesis of quinazoline 3-oxides and their derivatives has attracted considerable attention due to their reactivity as intermediates in the synthesis of quinazoline analogues and their ring-expanded derivatives. Despite this, there is no comprehensive review dedicated to the synthesis and chemical transformation of these biologically relevant azaaromatic oxides. This review aims to provide an up-to-date record of the synthesis of quinazoline 3-oxides and their chemical transformation. It is hoped that this information will help medicinal chemistry researchers to design and synthesize new derivatives or analogues to treat various diseases.

In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides

“…Cytotoxicity was measured in breast cancer (MCF-7), lung cancer (A549) and the HEK293-T cell lines (Cellonex Separation Scientific SA (Pty) Ltd. (Roodepoort, Johannesburg, South Africa) using the standard 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay [15] against doxorubicin and gefitinib as positive controls. Cells were cultured in sterile Dulbecco's Minimal Essential Medium (DMEM, Gibco) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin solution.…”

“…The DPPH radical scavenging assay was conducted following the procedure described in our previous study [15]. The test compounds and ascorbic acid at various concentrations (ranging from 0 µM to 50 µM) in DMSO were mixed with a solution of DPPH (0.20 mM) in methanol and incubated in the dark for 45 min.…”

“…The assay was conducted following the method described in our previous study [15]. A mixture of 10 mM sodium nitroprusside (20 µL), phosphate buffer (5 µL) and the test compound (5 µL) were incubated at 25 • C in a 96-well plate for 2.5 h. After incubation, 20 µL of Griess reagent (1.00 g of sulfanilic acid + 0.10 g naphthylethylene diamine dihydrochloride) was added to the previous mixture and allowed to stand for 30 min.…”

“…Structureactivity relationship analysis and molecular docking studies suggested that the presence of a halogen atom at the C-6 position and a 2-aryl group of these heteroaromatic N-oxides enhances the inhibitory effect against COX-2. Unlike the quinazoline 3-oxides, which have been extensively evaluated for biological properties [15], corresponding data for their 1,2-dihydroquinazoline 3-oxide precursors are considerably less documented [16,17]. The 1,2-dihydroquinazoline 3-oxides have previously been evaluated for cytotoxicity against the human promyelocytic leukaemia HL-60 and lymphoblastic leukaemia NALM-6 cell lines [16].…”

In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides

“…Cytotoxicity was measured in breast cancer (MCF-7), lung cancer (A549) and the HEK293-T cell lines (Cellonex Separation Scientific SA (Pty) Ltd. (Roodepoort, Johannesburg, South Africa) using the standard 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay [15] against doxorubicin and gefitinib as positive controls. Cells were cultured in sterile Dulbecco's Minimal Essential Medium (DMEM, Gibco) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin solution.…”

“…The DPPH radical scavenging assay was conducted following the procedure described in our previous study [15]. The test compounds and ascorbic acid at various concentrations (ranging from 0 µM to 50 µM) in DMSO were mixed with a solution of DPPH (0.20 mM) in methanol and incubated in the dark for 45 min.…”

“…The assay was conducted following the method described in our previous study [15]. A mixture of 10 mM sodium nitroprusside (20 µL), phosphate buffer (5 µL) and the test compound (5 µL) were incubated at 25 • C in a 96-well plate for 2.5 h. After incubation, 20 µL of Griess reagent (1.00 g of sulfanilic acid + 0.10 g naphthylethylene diamine dihydrochloride) was added to the previous mixture and allowed to stand for 30 min.…”

“…Structureactivity relationship analysis and molecular docking studies suggested that the presence of a halogen atom at the C-6 position and a 2-aryl group of these heteroaromatic N-oxides enhances the inhibitory effect against COX-2. Unlike the quinazoline 3-oxides, which have been extensively evaluated for biological properties [15], corresponding data for their 1,2-dihydroquinazoline 3-oxide precursors are considerably less documented [16,17]. The 1,2-dihydroquinazoline 3-oxides have previously been evaluated for cytotoxicity against the human promyelocytic leukaemia HL-60 and lymphoblastic leukaemia NALM-6 cell lines [16].…”

Assessment of Acute Toxicity of Quinazoline Derivative 3-[2-oxo-2-(4-Phenylpiperazine-1-yl)Ethyl]quinazoline-4(3h)-oh Active against Opportunistic Microorganisms

“…Синтезирован ряд хиназолиновых соединений с противоинфекционным действием: противовирусным, противогрибковым, противомалярийным, противомикробным, проявляющимся в отношении широкого спектра патогенных и условно-патогенных микроорганизмов [7][8][9]. Основными преимуществами данных соединений, наряду с широкой фармакологической активностью, является относительная простота их синтеза, а также возможность улучшения их свойств за счёт применения незначительных модификаций химической формулы [10,11]. Принимая во внимание вышеописанные сведения, перспективно исследование новых производных хиназолина как лекарственных кандидатов, одним из которых является субстанция 3-[2-оксо-2-(4-фенилпиперазин-1ил)этил]хиназолин-4(3h)-он (с лабораторным шифром VMA-10-21), синтезированная учёными Волгоградского государственного медицинского университета.…”

In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides

“…Cytotoxicity was measured in breast cancer (MCF-7), lung cancer (A549) and the HEK293-T cell lines (Cellonex Separation Scientific SA (Pty) Ltd. (Roodepoort, Johannesburg, South Africa) using the standard 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay [15] against doxorubicin and gefitinib as positive controls. Cells were cultured in sterile Dulbecco's Minimal Essential Medium (DMEM, Gibco) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin solution.…”

“…The DPPH radical scavenging assay was conducted following the procedure described in our previous study [15]. The test compounds and ascorbic acid at various concentrations (ranging from 0 µM to 50 µM) in DMSO were mixed with a solution of DPPH (0.20 mM) in methanol and incubated in the dark for 45 min.…”

“…The assay was conducted following the method described in our previous study [15]. A mixture of 10 mM sodium nitroprusside (20 µL), phosphate buffer (5 µL) and the test compound (5 µL) were incubated at 25 • C in a 96-well plate for 2.5 h. After incubation, 20 µL of Griess reagent (1.00 g of sulfanilic acid + 0.10 g naphthylethylene diamine dihydrochloride) was added to the previous mixture and allowed to stand for 30 min.…”

“…Structureactivity relationship analysis and molecular docking studies suggested that the presence of a halogen atom at the C-6 position and a 2-aryl group of these heteroaromatic N-oxides enhances the inhibitory effect against COX-2. Unlike the quinazoline 3-oxides, which have been extensively evaluated for biological properties [15], corresponding data for their 1,2-dihydroquinazoline 3-oxide precursors are considerably less documented [16,17]. The 1,2-dihydroquinazoline 3-oxides have previously been evaluated for cytotoxicity against the human promyelocytic leukaemia HL-60 and lymphoblastic leukaemia NALM-6 cell lines [16].…”

Assessment of Acute Toxicity of Quinazoline Derivative 3-[2-oxo-2-(4-Phenylpiperazine-1-yl)Ethyl]quinazoline-4(3h)-oh Active against Opportunistic Microorganisms

“…Синтезирован ряд хиназолиновых соединений с противоинфекционным действием: противовирусным, противогрибковым, противомалярийным, противомикробным, проявляющимся в отношении широкого спектра патогенных и условно-патогенных микроорганизмов [7][8][9]. Основными преимуществами данных соединений, наряду с широкой фармакологической активностью, является относительная простота их синтеза, а также возможность улучшения их свойств за счёт применения незначительных модификаций химической формулы [10,11]. Принимая во внимание вышеописанные сведения, перспективно исследование новых производных хиназолина как лекарственных кандидатов, одним из которых является субстанция 3-[2-оксо-2-(4-фенилпиперазин-1ил)этил]хиназолин-4(3h)-он (с лабораторным шифром VMA-10-21), синтезированная учёными Волгоградского государственного медицинского университета.…”

In Vitro α-Glucosidase and α-Amylase Inhibition, Cytotoxicity and Free Radical Scavenging Profiling of the 6-Halogeno and Mixed 6,8-Dihalogenated 2-Aryl-4-methyl-1,2-dihydroquinazoline 3-Oxides

“…Cytotoxicity was measured in breast cancer (MCF-7), lung cancer (A549) and the HEK293-T cell lines (Cellonex Separation Scientific SA (Pty) Ltd. (Roodepoort, Johannesburg, South Africa) using the standard 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay [15] against doxorubicin and gefitinib as positive controls. Cells were cultured in sterile Dulbecco's Minimal Essential Medium (DMEM, Gibco) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin solution.…”

“…The DPPH radical scavenging assay was conducted following the procedure described in our previous study [15]. The test compounds and ascorbic acid at various concentrations (ranging from 0 µM to 50 µM) in DMSO were mixed with a solution of DPPH (0.20 mM) in methanol and incubated in the dark for 45 min.…”

“…The assay was conducted following the method described in our previous study [15]. A mixture of 10 mM sodium nitroprusside (20 µL), phosphate buffer (5 µL) and the test compound (5 µL) were incubated at 25 • C in a 96-well plate for 2.5 h. After incubation, 20 µL of Griess reagent (1.00 g of sulfanilic acid + 0.10 g naphthylethylene diamine dihydrochloride) was added to the previous mixture and allowed to stand for 30 min.…”

“…Structureactivity relationship analysis and molecular docking studies suggested that the presence of a halogen atom at the C-6 position and a 2-aryl group of these heteroaromatic N-oxides enhances the inhibitory effect against COX-2. Unlike the quinazoline 3-oxides, which have been extensively evaluated for biological properties [15], corresponding data for their 1,2-dihydroquinazoline 3-oxide precursors are considerably less documented [16,17]. The 1,2-dihydroquinazoline 3-oxides have previously been evaluated for cytotoxicity against the human promyelocytic leukaemia HL-60 and lymphoblastic leukaemia NALM-6 cell lines [16].…”

Assessment of Acute Toxicity of Quinazoline Derivative 3-[2-oxo-2-(4-Phenylpiperazine-1-yl)Ethyl]quinazoline-4(3h)-oh Active against Opportunistic Microorganisms

“…Синтезирован ряд хиназолиновых соединений с противоинфекционным действием: противовирусным, противогрибковым, противомалярийным, противомикробным, проявляющимся в отношении широкого спектра патогенных и условно-патогенных микроорганизмов [7][8][9]. Основными преимуществами данных соединений, наряду с широкой фармакологической активностью, является относительная простота их синтеза, а также возможность улучшения их свойств за счёт применения незначительных модификаций химической формулы [10,11]. Принимая во внимание вышеописанные сведения, перспективно исследование новых производных хиназолина как лекарственных кандидатов, одним из которых является субстанция 3-[2-оксо-2-(4-фенилпиперазин-1ил)этил]хиназолин-4(3h)-он (с лабораторным шифром VMA-10-21), синтезированная учёными Волгоградского государственного медицинского университета.…”