Series Of Quinazolines Research Articles

Discovery of A Novel Series of Quinazoline-Thiazole Hybrids as Potential Antiproliferative and Anti-Angiogenic Agents.

Considering the pivotal role of angiogenesis in solid tumor progression, we developed a novel series of quinazoline-thiazole hybrids (SA01-SA07) as antiproliferative and anti-angiogenic agents. Four out of the seven compounds displayed superior antiproliferative activity (IC50 =1.83-4.24 µM) on HepG2 cells compared to sorafenib (IC50 = 6.28 µM). The affinity towards the VEGFR2 kinase domain was assessed through in silico prediction by molecular docking, molecular dynamics studies, and MM-PBSA. The series displayed a high degree of similarity to sorafenib regarding the binding pose within the active site of VEGFR2, with a different orientation of the 4-substituted-thiazole moieties in the allosteric pocket. Molecular dynamics and MM-PBSA evaluations identified SA05 as the hybrid forming the most stable complex with VEGFR2 compared to sorafenib. The impact of the compounds on vascular cell proliferation was assessed on EA.hy926 cells. Six compounds (SA01-SA05, SA07) displayed superior anti-proliferative activity (IC50 = 0.79-5.85 µM) compared to sorafenib (IC50 = 6.62 µM). The toxicity was evaluated on BJ cells. Further studies of the anti-angiogenic effect of the most promising compounds, SA04 and SA05, through the assessment of impact on EA.hy296 motility using a wound healing assay and in ovo potential in a CAM assay compared to sorafenib, led to the confirmation of the anti-angiogenic potential.

A TEMPO promoted tandem reaction of 2-aminobenzophenones and benzylamines under electrochemical conditions.

This study describes the efficient synthesis of quinazolines promoted by TEMPO via electro-catalysis with 2-aminobenzophenones and benzylamines. The method exhibited remarkable chemoselectivity under mild reaction conditions. A series of quinazolines could be obtained in moderate to good yields. In addition, control experiments were carried out to verify the reaction mechanism. Furthermore, the synthesis on the gram scale was conducted successfully to give the target product.

Spectrophotometric and infra-red analyses of azo reactive dyes derived from 2-methyl-3-(2’- methylphenyl)-6-arylazo-4- oxoquinazoline

Ultraviolet-visible and infrared spectroscopic techniques were used to determine the possible composition and functional groups present in a series of quinazoline based mono azo reactive dyes (DM1-5) which was prepared by coupling 2-methyl-3-(2’- methylphenyl)-6-arylazo-4-oxoquinazoline diazonium solution with five (5) cyanurated coupling components . The result of visible absorption spectra showed that the λmax obtained for each dye depends on the coupling component used and that the λmax tend to shift to the shorter wavelength (hypsochromic shift) as the auxochromes appear to have influence on the absorption peak of the dyes... The IR spectral showed all the characteristics and representative of azo reactive dyes, with characteristic band in the range of 3400 - 3309 cm-1 indicating the presence of -OH and –NH stretching vibration, 1382 - 1049 cm-1 for the presence of –C-N, 1141-1010 cm-3 for –S=0 and 925 - 56 cm-1 for the presence of - C-Cl . The azo band occurred in the region of 1458 - 1411 cm-1 which is due to stretching vibration of the -N=N- group. A strong band at 1643 - 1604 cm-1 is due to the stretching vibration of -C=O group of the quinazoline compound. However, the IR spectrum did not actually reveal the chemical structure of the reactive dyes being studied. Further studies could be conducted using GCMS and NMR spectroscopy to confirm the structure of the dyes.

Synthesis, Computational Study of β-lactam Derivatives Bearing Quinazoline Schiff Bases as Anthelmintics

Background: Infections caused by parasites continue to pose a risk to both human and animal health. The most popular drug classes for treating these infections include thiabendazole, imidazothiazoles, levamisole, and avermectins (obtained from the fermentation products of Streptomyces avermitilis). The majority of bacteria that we come across in any form of infection are successfully combatted by β- lactam medicines. Similar to the majority of treatments, problems with treatment resistance to these drugs have evolved over time, necessitating the development of new anthelmintic medications. This study aims to investigate a series of quinazoline-bearing β-lactam rings as potent anthelmintic agents. Methods: The new series of quinazoline bearing β-lactam was synthesized via reaction of 5-bromo anthranilic acid with acetic anhydride to produce 6-bromo-2-methyl-4H-benzo (1,3) oxazin-4-one which was then converted into 3-amino-6-bromo-2-methylquinazolin-4(3H)-one by the reaction of hydrazine hydrate in the presence of anhydrous pyridine. The resultant intermediate then goes through a Schiff reaction with various aromatic aldehydes, followed by reflux with triethylamine and chloroacetyl chloride. Results: Structural assignments of these compounds have been made by elemental analysis, FTIR,1HNMR and Mass spectral data and the purity of the compounds was determined by TLC. Molecular docking studies showed the effective binding of synthesized derivatives with tubulin in comparison to the orientation of standard drugs. The anthelmintic activities of all the synthesized compounds were evaluated separately for their possible using common Indian earthworm Pheritima posthuma. Conclusion: A total of ten derivatives of quinazoline bearing β-lactam ring were designed, synthesized and evaluated against the Indian earthworm Pheritima posthuma. Out of ten derivatives, SQD2 and SQD6, showed promising anthelmintic activity when compared with standard drugs albendazole and piperazine citrate.

Design, Synthesis, and Biological Evaluation of Heterocyclic-Fused Pyrimidine Chemotypes Guided by X-ray Crystal Structure with Potential Antitumor and Anti-multidrug Resistance Efficacy Targeting the Colchicine Binding Site.

Herein, a series of quinazoline and heterocyclic fused pyrimidine analogues were designed and synthesized based on the X-ray co-crystal structure of lead compound 3a, showing efficacious antitumor activities. Two analogues, 15 and 27a, exhibited favorable antiproliferative activities, which were more potent than lead compound 3a by 10-fold in MCF-7 cells. In addition, 15 and 27a exhibited potent antitumor efficacy and tubulin polymerization inhibition in vitro. 15 reduced the average tumor volume by 80.30% (2 mg/kg) in the MCF-7 xenograft model and 75.36% (4 mg/kg) in the A2780/T xenograft model, respectively. Most importantly, supported by structural optimization and Mulliken charge calculation, X-ray co-crystal structures of compounds 15, 27a, and 27b in complex with tubulin were resolved. In summary, our research provided the rational design strategy of colchicine binding site inhibitors (CBSIs) based on X-ray crystallography with antiproliferation, antiangiogenesis, and anti-multidrug resistance properties.

In silico design of novel quinazoline-based compounds as potential Mycobacterium tuberculosis PknB inhibitors through 2D and 3D-QSAR, molecular dynamics simulations combined with pharmacokinetic predictions

Serine/threonine protein kinase B (PknB) is essential to Mycobacterium tuberculosis (M. tuberculosis) cell division and metabolism and a potential anti-tuberculosis drug target. Here we apply Hologram Quantitative Structure Activity Relationship (HQSAR) and three-dimensional QSAR (Comparative Molecular Similarity Indices Analysis (CoMSIA)) methods to investigate structural requirements for PknB inhibition by a series of previously described quinazoline derivatives. PknB binding of quinazolines was evaluated by molecular dynamics (MD) simulations of the catalytic domain and binding energies calculated by Molecular Mechanics/Poisson Boltzmann Surface Area (MM-PBSA) and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) methods. Evaluation of a training set against experimental data showed both HQSAR and CoMSIA models to reliably predict quinazoline binding to PknB, and identified the quinazoline core and overall hydrophobicity as the major contributors to affinity. Calculated binding energies also agreed with experiment, and MD simulations identified hydrogen bonds to Glu93 and Val95, and hydrophobic interactions with Gly18, Phe19, Gly20, Val25, Thr99 and Met155, as crucial to PknB binding. Based on these results, additional quinazolines were designed and evaluated in silico, with HQSAR and CoMSIA models identifying sixteen compounds, with predicted PknB binding superior to the template, whose activity spectra and physicochemical, pharmacokinetic, and anti-M. tuberculosis properties were assessed. Compound, D060, bearing additional ortho- and meta-methyl groups on its R2 substituent, was superior to template regarding PknB inhibition and % caseum fraction unbound, and equivalent in other aspects, although predictions identified hepatotoxicity as a likely issue with the quinazoline series. These data provide a structural basis for rational design of quinazoline derivatives with more potent PknB inhibitory activity as candidate anti-tuberculosis agents.

Bicyclic Heterocyclic Replacement of an Aryl Amide Leading to Potent and Kinase-Selective Adaptor Protein 2-Associated Kinase 1 Inhibitors.

Adaptor protein 2-associated kinase 1 (AAK1) is a serine/threonine kinase that was identified as a therapeutic target for the potential treatment of neuropathic pain. Inhibition of AAK1 in the central nervous system, particularly within the spinal cord, was found to be the relevant site for achieving an antinociceptive effect. We previously reported that compound 7 is a brain-penetrant, AAK1 inhibitor that showed efficacy in animal models for neuropathic pain. One approach we took to improve upon the potency of 7 involved tying the amide back into the neighboring phenyl ring to form a bicyclic heterocycle. Investigation of the structure-activity relationships (SARs) of substituents on the resultant quinazoline and quinoline ring systems led to the identification of (S)-31, a brain-penetrant, AAK1-selective inhibitor with improved enzyme and cellular potency compared to 7. The synthesis, SAR, and in vivo evaluation of a series of quinazoline and quinoline-based AAK1 inhibitors are described herein.

The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study.

In order to investigate for a new effective and safe anticancer drug, we synthesized a novel series of quinazoline containing biologically active substituted-sulfonamide moiety at 3- position 4a–n. The structure of the newly prepared compounds was proved by microanalysis, IR, 1H-NMR, 13C-NMR and mass spectral data. All the synthesized compounds were evaluated for their in vitro cytotoxic activity in numerous cancer cell lines including A549, HepG-2, LoVo and MCF-7 and normal HUVEC cell line. The two most active compounds 4d and 4f were then tested for their apoptosis induction using DNA content and Annexin V-FITC/PI staining. Moreover, apoptosis initiation was also confirmed using RT-PCR and Western blot. To further understand the binding preferences of quinazoline sulfonamides, docking simulations were used. Among the fourteen new synthesized compounds, we found that compounds 4d and 4f exerted the strongest cytotoxicity against MCF-7 cells with an IC50 value of 2.5 and 5 μM, respectively. Flow cytometry data revealed the ability of compounds 4d and 4f to mediate apoptosis and arrest cell cycle growth at G1 phase. Furthermore, RT-PCR and Western blot results suggested that both 4d and 4f activates apoptotic cell death pathway in MCF-7 cells. Molecular docking assessments indicated that compounds 4d and 4f fit perfectly into Bcl2’s active site. Based on the biological properties, we conclude that both compounds 4d and 4f could be used as a new type of anticancer agent, which provides a scientific basis for further research into the treatment of cancer.

In-silico activity prediction, structure-based drug design, molecular docking and pharmacokinetic studies of selected quinazoline derivatives for their antiproliferative activity against triple negative breast cancer (MDA-MB231) cell line

BackgroundCancer is a major health threat especially in unindustrialized nations. It surpasses coronary diseases and takes the number one killer position as a result of different global wide influences. Among many breast cancer substrates, triple-negative breast cancer (TNBC) is particularly devastating because it rapidly metastasize to other parts of the body, with a high risk of earlier recession and mortality.ResultIn this research work, four (4) quantitative structure activity relationship (QSAR) models were developed using a series of quinazoline derivatives with activities against triple negative breast cancer cell line (MDA-MB231), model 1 was selected due to its statistical fitness with the following validation parameters: R2 = 0.875, Q2 = 0.837, R2 − Q2 = 0.038, Next test set = 5, and R2ext = 0.655. Molecular docking studies was performed for the quinazoline series as well as the reference drug (Gefitinib) and the active site of the epidermal growth factor receptor (EGFR) (pdb id = 3ug2). Eight compounds (6, 10, 13, 16, 17, 18, 19 and 20) were observed to have better docking score docking scores relative to Gefitinib. Compound number nineteen from the training set (pred pIC50 = 5.67, Residual = − 0.04 and MolDock score = − 123.238) was identified as the best compound since it has the best Moldock score and was excellently predicted by the selected model with least residual value, Hence was adopted as template for the design of Ten (10) new novel compounds with better activities and better docking scores. The inhibitive activities of the designed compounds were predicted by the selected model and most of them possess an improved activity relative to the template compound (19). The designed compounds were also redocked on to active pocket of the EGFR receptor and it was observed that they displayed better docking scores compared to the Template and the reference drug (Gefitinib) utilized in the design. Furthermore, the designed compounds were subjected to ADMET and drug-likeness studies using SWISSADME and pkCSM online web tools and they were observed to be pharmacologically active, easily synthesized and do not violate the Lipinski’s rule of five.ConclusionHence, the designed compounds can be employed as inhibitors of MDA-MB231 cell line after passing through in vivo and in vitro evaluation.

Cucurbit[6]uril supported β-Ni(OH)2 nanoparticles as a heterogeneous catalyst for the synthesis of quinazolines via acceptorless dehydrogenative coupling of alcohols with nitriles

Synthesis of a series of quinazolines using β-Ni(OH)2-CB[6] as a heterogeneous nanocatalyst.

Investigation of Janus Kinase (JAK) Inhibitors for Lung Delivery and the Importance of Aldehyde Oxidase Metabolism

The Janus family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) play an essential role in the receptor signaling of cytokines that have been implicated in the pathogenesis of severe asthma, and there is emerging interest in the development of small-molecule-inhaled JAK inhibitors as treatments. Here, we describe the optimization of a quinazoline series of JAK inhibitors and the results of mouse lung pharmacokinetic (PK) studies where only low concentrations of parent compound were observed. Subsequent investigations revealed that the low exposure was due to metabolism by aldehyde oxidase (AO), so we sought to identify quinazolines that were not metabolized by AO. We found that specific substituents at the quinazoline 2-position prevented AO metabolism and this was rationalized through computational docking studies in the AO binding site, but they compromised kinome selectivity. Results presented here highlight that AO metabolism is a potential issue in the lung.

Synthesis, in vitro cytotoxic, anti-Mycobacterium tuberculosis and molecular docking studies of 4-pyridylamino- and 4-(ethynylpyridine)quinazolines

• Successful synthesis of compounds of the series 4-chloro-, 4-(pyridylamino)- and 4-(ethynylpyridine)-quinazoline. • Positive results from the Alamar Blue assay ( Mtb H37Rv strain) which revealed promising MIC 90 ranging from <0.7 to >125 µM. • Candidate compounds were inductively docked into the 3ZXR enzyme and the more prominent hydrogen bond is between Nitrogen of the pyridine ring moiety of the 5 and 6 series with an OH group of SER280. • A metal coordination between the methoxy benzene moiety of compounds in the 6 series and Mg 2+ is also observed, explaining the SAR of these compounds to MtGS enzyme. A series of 4-(pyridylamino)- and 4-(ethynylpyridine)quinazolines were successfully prepared via Sonogashira cross-coupling and dechloroamination reactions on the C(4)-Cl position of the requisite 2-(p-phenyl)-4-chloroquinazolines. The prepared compounds were characterized by means of 1 H- and 13 C-NMR, FT-IR and mass spectrometry techniques. The structure of 2-(4-chlorophenyl)-4-(2-(pyridin-4-yl) ethynyl) quinazoline from the 4-(ethynylpyridine) series was confirmed by single crystal X-ray analysis which indicates monoclinic crystal system and P21/c space group. Compounds from the 4-chloro-, 4-(pyridylamino)- and 4-(ethynylpyridine)-quinazoline series were evaluated for anti- Mycobacterium tuberculosis ( Mtb ) properties in vitro employing rifampicin as a reference drug. The results from the Alamar Blue assay ( Mtb H37Rv strain) revealed promising MIC 90 ranging from <0.7 to >125 µM. The cytotoxicity of the synthesised compounds was tested against the Raw 264.7 microphage cell line at a maximum concentration of 50 µM. The possible mode of interaction against the Mtb was theoretically explained through molecular 3ZXR protein and the more prominent hydrogen bond is observed between the nitrogen of the pyridine ring moiety of the 5 and 6 series with OH group of SER280. Also, a metal coordination between the methoxy benzene moiety of compound 6e and Mg 2+ is also observed, explaining the SAR of these compounds to MtGS.

Synthesis and Evaluation of Anticonvulsant Activity of Some Quinazoline Analogues

Aim: A new series of Quinazoline 4(3H)-one derivative were prepared by reacting quinazoline 4(3H)-one hydrazide with substituted aromatic aldehydes. Quinazoline is used as a potent pharmacological agent with various biological activities such as antimicrobial, antiviral, antitumor, convulsion, anxiety, anti-inflammatory, and analgesic. In this background, we have synthesized a series of Quinazoline 4(3H)-one derivatives (4a-4f) and screened for their anticonvulsant activity. &#x0D; Methods: In this work, Schiff bases were prepared by treating quinazoline 4(3H)-one hydrazide with aromatic aldehydes. Six compounds (4a-4f) were screened for anticonvulsant activity by Isoniazid (INH) and Pentylenetetrazole (PTZ) induced convulsions in mice.&#x0D; Results: All the compounds were given satisfactory reaction yields that representing the efficiency of the employed synthetic route. In INH induced convulsion model, delayed the onset of convulsion significantly 4a, 4b, 4d, 4e, 4f when compared to an induction control group. Whereas delayed onset of convulsion was non-significant for 4c. In PTZ induced convulsion model, delayed the onset of convulsion significantly 4a, 4d, 4e, 4f when compared to induction control group. Whereas delayed onset of convulsion was non-significant for 4b and 4c.&#x0D; Conclusion: This indicates the anticonvulsant activity to these derivatives which might be due to potentiating GABA activity in the CNS. This anticonvulsant activity was due to presence of electron-donating group like OH, NH2, OCH3 and electron-withdrawing group like CF3 at 2nd and 4th position of aromatic ring attached to hydrazide.

Palladium-catalyzed carbonylative synthesis of quinazolines: Silane act as better nucleophile than amidine

Abstract A palladium-catalyzed reductive carbonylation reaction has been developed for the synthesis of quinazolines. With N-(2-iodophenyl)benzimidamide as starting materials, a series of quinazolines were obtained through the aromatic aldehyde intermediates in moderate to good yields with good functional group compatibilities. In this system, silane act as better nucleophile than amidine.

Quinazoline clubbed thiazole and 1,3,4-oxadiazole heterocycles: synthesis, characterization, antibacterial evaluation, and molecular docking studies

In search of potent antibacterial agents, a series of novel quinazolines, bearing thiazole and 1,3,4-oxadiazole heterocycles 6a–j (3-(4-methyl-5-(4-((arylamino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)thiazol-2-yl)-2-phenylquinazolin-4(3H)-ones) were synthesized and the structures of the compounds were elucidated by standard spectroscopic techniques. In order to evaluate their antibacterial potential, the antibacterial assay of synthesized compounds 6a–j was performed against MTCC strains, wherein compounds 6d (3-(4-methyl-5-(4-(((4-nitrophenyl)amino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)thiazol-2-yl)-2-phenylquinazolin-4(3H)-one) (Escherichia coli, MIC = 100 µg mL−1) and 6e (3-(5-(4-(((2-chlorophenyl)amino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-methylthiazol-2-yl)-2-phenylquinazolin-4(3H)-one) (E. coli, MIC = 62.5 µg mL−1) were most active against Gram-negative bacteria while compound 6f (3-(5-(4-(((4-chlorophenyl)amino)methyl)-5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)-4-methylthiazol-2-yl)-2-phenylquinazolin-4(3H)-one) (Staphylococcus aureus, MIC = 50 µg mL−1) was most active against Gram-positive bacteria. Furthermore, molecular docking simulation was performed to determine the probable binding mode and affinity of the synthesized compounds toward bacterial DNA gyrase. The preliminary results pave the way for further designing the thiazole based 1,3,4-oxadiazoles heterocycles for enhancing their potency as antibacterial agents.

A Diverse Range of Hemozoin Inhibiting Scaffolds Act on Plasmodium falciparum as Heme Complexes.

A diverse series of hemozoin-inhibiting quinolines, benzamides, triarylimidazoles, quinazolines, benzimidazoles, benzoxazoles, and benzothiazoles have been found to lead to exchangeable heme levels in cultured Plasmodium falciparum (NF54) that ranged over an order of magnitude at the IC50. Surprisingly, less active compounds often exhibited higher levels of exchangeable heme than more active ones. Quantities of intracellular inhibitor measured using the inoculum effect exhibited a linear correlation with exchangeable heme, suggesting formation of heme-inhibitor complexes in the parasite. In an effort to confirm this, the presence of a Br atom in one of the benzimidazole derivatives was exploited to image its distribution in the parasite using electron spectroscopic imaging of Br, an element not naturally abundant in cells. This showed that the compound colocalized with iron, consistent with its presence as a heme complex. Direct evidence for this complex was then obtained using confocal Raman microscopy. Exchangeable heme and inhibitor were found to increase with decreased rate of killing, suggesting that slow-acting compounds have more time to build up exchangeable heme complexes. Lastly, some but not all compounds evidently cause pro-oxidant effects because their activity could be attenuated with N-acetylcysteine and potentiated with t-butyl hydroperoxide. Collectively, these findings suggest that hemozoin inhibitors act as complexes with free heme, each with its own unique activity.

Light-driven photoswitching of quinazoline analogues of combretastatin A-4 as an effective approach for targeting skin cancer cells.

A novel quinazoline series of photoswitchable combretastatin A-4 (CA-4) analogues were synthesized and their photochemical properties and antiproliferative activity against A431 epidermoid carcinoma cells were studied. It was found that quinazoline analogues, in contrast to the majority of the known CA-4, exhibit high antiproliferative activity in the E-form as well. Photoswitching of the E-form to the Z-form resulted in a multiple (9-fold) increase in antiproliferative activity. 1H NMR monitoring showed that these compounds are very resistant to UV (λ = 365 nm) or sunlight irradiation and do not undergo photodegradation with a loss of antiproliferative activity that is inherent in heterocyclic analogues of CA-4. Similar photoswitching and an increase in antiproliferative activity are observed on exposure to sunlight. A selected compound (1a-Z51) in sub-micromolar concentrations induced apoptosis in A431 cells, while rad50/ATM/p53 were not involved in cell death. The growth of A431 cells was significantly inhibited after combination treatment with compound 1a-Z51 and chemotherapy drugs (cisplatin or 5-fluorouracil). In summary, the quinazoline analogues of CA-4 represent a promising strategy to achieve a photoswitchable potency for the treatment of cancers, including the development of combination therapies.

Design, synthesis and anti-influenza A virus activity of novel 2,4-disubstituted quinazoline derivatives

Four 2,4-disubstituted quinazoline series containing various amide moieties were designed and synthesized as new anti-influenza A virus agents using the strategies of bio-isosterism and scaffold hopping. Many of them exhibit potent in vitro anti-influenza A virus activity and low cytotoxicity (CC50: >100 μM). Particularly, compounds 10a5 and 17a show better activity (IC50: 3.70–4.19 μM) and higher selective index (SI: >27.03, >23.87, respectively) against influenza A/WSN/33 virus (H1N1), opening a new direction for quinazoline derivatives in anti-influenza A virus field.

Utilization of 2-substituted 3, 1-benzoxazin-4-ones in synthesis of some quinazoline annulated derivatives

In this study, a new series of quinazoline and their annulated derivatives have been synthesized. A number of quiazolinone derivatives substituted at position-3 were prepared from 3, 1-benzoxazinone by the treatment of 3,1-benzoxazinone with different nitrogen nucleophiles such as, hydrazine hydrate, phenylhydrazine, ethanolamine, and cyano acetohydrazide afforded the quinazolinone derivatives 7–11. The reaction of hydrazide derivative 5 with aromatic aldehydes gave the Schiff’s bases derivative 16a–c. Some of the synthesized compounds were tested against the breast cancer cell line (MCF-7). The structures of all the newly synthesized compounds were established based on IR, 1H, 13C NMR, mass spectral data, and elemental analyses.

Synthesis and in vitro Cytotoxicity Study of Novel 4-Substituted Quinazolines Encompassed with Thiazolidinone and Azetidinone

A series of quinazolines encompassed with thiazolidinone and azetidinone have been synthesized and evaluated for their antioxidant, anticancer and DNA binding studies. All the synthesized compounds were characterized by IR, 1H &amp; 13C NMR and mass spectra. Antioxidant activity was carried out using % free radical scavenging by DPPH assay. Compounds 4b, 5b and 5d have shown better antioxidant activity (60, 67 and 66%, respectively) among the tested compounds. Compounds having % free radical scavenging activity more than 55% were evaluated for anticancer activity by MTT assay towards cell lines A-549 (lung carcinoma) and MDA-231 (human breast cancer). Results revealed that the tested compounds exhibited moderate to low anticancer activity. Further, DNA binding activity was studied by absorption titration method for all the synthesized compounds, and compound 5b showed a good binding constant of 70.05 and % hyperchromicity of 82.93%.