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In this study, a new series of quinazolinone-1,2,3-triazole-acetamide hybrids 8a–m, using by molecular hybridization of the potent α-glucosidase inhibitor pharmacophores, was designed and evaluated against carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase. All the synthesized compounds with IC50 values in the range of 45.3 ± 1.4 µM to 195.5 ± 4.7 µM were significantly more potent than standard inhibitor against α-glucosidase, while these compounds were not active against α-amylase in comparison to standard inhibitor. Representatively, compound 8a with IC50 = 45.3 ± 1.4 µM was around 17 times more potent than standard inhibitor acarbose (IC50 = 750.0 ± 12.5 µM). The inhibition kinetic analysis of the compound 8a indicated that this compound was a competitive α-glucosidase inhibitor. Molecular modeling analysis confirmed that the most potent inhibitors 8a and 8b well accommodated in the modeled α-glucosidase active site and it was also revealed that these compounds formed stable inhibitor–receptor complexes with the α-glucosidase in comparison to acarbose. In silico pharmacokinetic and toxicity of the most potent compounds were evaluated and obtained results were compared with acarbose. Furthermore, the most potent compounds were also evaluated against human normal cells and no cytotoxicity was observed.

Quinazolin-4-ones linked to 1,2,3-triazol (10) were identified as inhibitors of the bisphosphonate BPH-700 transcriptional factor from a high throughput screen. A series of 1,4-disubstituted triazoles (10a–j) were synthesized by the Cu-catalyzed azide-alkyne cyclo addition of 5-methoxy-2-nitro-4-(prop-2-yn-1-yloxy) benzamide (6) with various substituted azido benzenes (7) in the presence of CuSO4 under aerobic conditions followed by click reaction with substituted aldehydes. The target compounds were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv by Broth micro dilution method using Lowenstein Jensen medium (LJ) (MIC

A series of novel quinazolinone derivatives bearing a disulfide bond were designed and synthesized. Their in vitro antiproliferative activities were evaluated using CCK-8 assay against SMMC-7721, Hela, A549 and MCF-7 human cancer cell lines and normal cell lines L929. The preliminary bioassay results demonstrated that all compounds 7a–7h, 8a–8h and 9a–9h exhibited antiproliferation with various degrees, and some compounds showed better effects than positive control 5-fluorouracil against different cancer cell lines. Among these compounds, 8c and 9f showed significant antiproliferative activity against SMMC-7721 cells with IC50 values of 2.88 and 2.56 μM, respectively. In Hela cells, compounds 9c and 9d showed highly effective biological activity with IC50 values of 3.16 and 2.68 μM, respectively. Compounds 7a and 9a exhibited good inhibitory effect against A549 cells with IC50 values of 3.53 and 3.54 μM, respectively. In MCF-7 cells, compounds 7e, 8e and 9e displayed excellent activity with IC50 values of 1.26, 1.12 and 1.85 μM, respectively. Besides, most of the tested compounds showed low cytotoxic effect against the normal cell lines L929. Biological evaluation indicated that all the tested compounds possessed antibacterial activity with certain degrees.

A series of quinazoline-2,4,6-triamine (quinazoline) and 2,6-diaminoquinazolin-4(3H)-one (quinazolinone) derivatives were designed, synthesized and evaluated as cytotoxic agents in three cancer cell lines (HCT-15, SKOV-3, and MDA-MB-231) using conventional MTT assay. Of the tested compounds, only eleven quinazoline derivatives showed activity against all the tested cell lines, at 24 h of exposure. Among them, the compounds 3e and 3f exhibited the highest cytotoxic activity, with the most important IC50 values ranging from 4.5 to 15.5 μM. They were more active than the reference drugs (Gefitinib, PD153035) which showed IC50 values ranging between 19.4 and 48.8 μM. These compounds open new possibilities for preparing novel analogous of quinazoline as antitumor agents.

New series of 3-(3-trifluoromethylphenyl)-6-iodo-4(3H)-quinazolinone derivatives bearing thiosemicarbazones, pyrazoles, azomethine moieties at C-2 were synthesized. The obtained products were screened for their expected anticancer activity against; human liver cancer cell line (HepG2), breast cancer cell line (MCF-7) and human lung adenocarcinoma epithelial cell line (A549) tumor cell lines. Cytotoxicity of the synthesized compounds showed good IC50 for some products in comparison with the standard drug, doxorubicin. On the other hand, antiviral activity of the synthesized products against H5N1 showed moderate to weak activity compared to Zanamivir reference drug.

The present work describes the newly synthesized series of 4-(3H)-quinazolinone derivatives of hydrazones 5(a–j) starting from benzoxazine (4) by conventional method and substituted hydrazones 3(a–j) from substituted benzaldehydes and hydrazine hydrate. The reaction mixture was refluxed using ethanol as a solvent. All the synthesized compounds were obtained in good yields. The structures of all compounds have been deduced on the basis of spectroscopy and elemental analysis. The synthesized compounds 5(a–j) were screened for their potential in vivo anti-inflammatory activity using carrageenan-induced paw edema model and in vitro antibacterial activity against various strains of gram-positive and gram-negative bacteria.

2-(2-Chloroquinolin-3-yl)-3-(substituted phenyl/pyridinyl)quinazolin-4(3H)-one derivatives 5a–m were synthesized in good yield using conventional as well as microwave heating conditions in presence of l-proline as a catalyst. Synthetic conditions were optimized using an orthogonal array system of Taguchi’s design. The structure of synthesized quinazolinone compounds 5a–m was established with the help of physico-chemical analysis and various spectroscopic techniques like FT-IR, mass, 1H-NMR and 13C-NMR. Further, all the synthesized compounds were screened for their antimicrobial (antibacterial, antifungal and antimalarial) activities. The results of antimicrobial screening showed that compounds 4g, 4j, 4m, 5e and 5g have good activity against bacterial species, whereas compounds 4d, 4g, 4m, 5b, 5d and 5g have good activity against malaria pathogen. In addition to this, compounds 4i, 4j and 4m exhibited good to moderate activity against fungal strains.

The guanidine functionality has been found in numerous biologically active natural products and several drugs. We have, therefore, directed some of our efforts to synthesize analogs of 2-aminopyrimidine, a guanidine-containing six-membered heterocyclic scaffold, using microwave irradiation. The synthesized compounds have shown structural similarity to ispinesib, a quinazolinone-based KSP inhibitor that has already entered clinical trials. Molecular docking study was carried out to understand the binding modes of these newly synthesized compounds. The results of docking studies showed that these compounds interact with the same active site residues like ispinesib. From the molecular docking study, it was confirmed that these compound might be act as a potential candidate for KSP inhibition. Further lead optimization of drug-like properties was evaluated through in silico predictions by ADMET predictor™ software. The blood brain barrier penetration for both the synthesized compounds is predicted to be high compared to ispinesib. Hence, it is predicted that these compounds have tendency to treat the glioblastoma-like brain cancers. Hence a combination of in silico ADMET studies and molecular docking can help to improve prediction success and these compounds might be act as a potential candidate for KSP inhibition.

In view of their expected anticonvulsant activity, some novel derivatives of 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones (4–14) were synthesized, evaluated for their anticonvulsant activity by the maximal electroshock-induced seizure and subcutaneous pentylenetetrazole tests. The neurotoxicity was assessed using rotorod test. All the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 5, 6, and 8 proved to be the most potent compounds of this series with relatively low neurotoxicity and low toxicity in the median lethal dose test when compared with the reference drugs. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogs.

A novel series of 4-(amino or acetamido)-N-{[3-(substituted aryl)-4-oxo-3,4-dihydroquinazolin-2-yl]-methyl}benzenesulfonamide derivatives (1–19) were designed to assimilate 4-quinazolone and sulfonamide moieties in a single molecular framework. To derive entitled hybrid entities with structural diversity, an efficient multi-step synthetic approach initiated from glycine was developed, which involves milder conditions for emphasizing steps viz., reaction in aqueous-media, phosphazo-method of condensation, base mediated selective ester-cleavage, along with key-step, rapid and improved Grimmel’s hetero-cyclization method. The structure of the synthesized compounds was confirmed by physico-chemical characteristics and spectroscopic investigations. All these compounds were screened for their in vitro antimicrobial activity. The minimum inhibitory concentrations of the synthesized compounds against various bacteria (S. aureus, B. cereus, E. coli, K. pneumonia, P. aeruginosa) and fungus (A. niger, C. albicans) was measured by broth microdilution assay. Further, results on the preliminary biological activity indicated that most of the screened compounds have displayed varied degree of inhibitory actions.

A series of 2-(substituted-phenyl)-3-(((3-(pyridin-4-yl)-1-(p-tolyl)-1H-pyrazol-4-yl)methylene)amino)-quinazolin-4(3H)-ones have been synthesized. The structures of the synthesized compounds were assigned on the basis of IR, 1H NMR, 13C NMR, and mass spectral data, while their abilities to inhibit growth of Mycobacterium tuberculosis in vitro have been determined. The results show that compounds 5a, 5c, 5d, 5g, and 5k exhibited excellent antitubercular activity with percentage inhibition of 96, 90, 94, 93, and 92, respectively at a minimum inhibitory concentration (MIC) of 6.25 μg/mL. From the secondary screening, the actual MIC of compounds 5a, 5c, 5d, 5g, and 5k are

A new series of quinazoline analogs was designed, synthesized, and evaluated for their anticonvulsant activity. Compounds 6, 12, 21, 36, 37, and 38 showed 70–100 % protection against PTZ-induced seizures acting as GABAA receptor agonists. Compound N-(3,4,5,6-tetrachloro-phthalimido)-2-[(3-phenyl-4-oxo-6-methyl-3H-quinazolin-2-yl)-thio]acetamide (12) representing the moderate active compounds and 2-[6-iodo-4-oxo-2-(thiophen-2-yl)-quinazolin-3(4H)-yl]-isoindoline-1,3-dione (38) representing the remarkably active compounds in this stud, showed ED50 values of 457 and 251 mg/kg; TD50 values of 562 and 447 mg/kg; PI values of 1.22 and 1.78, LD50 values of 1,288 and 1,380 mg/kg, and TI values of 2.82 and 5.50, respectively. Compound 38 proved to be almost twofold more active than the standard drug sodium valproate.

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 used were NCI (human lung cancer cell), MCF 7 (Breast cancer cell), and HEK 293 (Normal epidermal kidney cell). Result of screening on cell line showed moderate to good anticancer activity for all the compounds. Compound 3d (IC50 = 1.1 ± 0.03 μM) was found to be the most active compared to standard methotrexate (IC50 = 2.20 ± 0.18 μM) and 5-florouracil (IC50 = 2.30 ± 0.49 μM). Structure activity relationship of synthesized analogs suggested that the presence of NH linker with aryl moiety at the third position of quinazolinone ring was important for potent anticancer activity. Electron donating group on phenyl ring at the third position of quinazolinone ring gave better anticancer activity then unsubstituted phenyl and electron withdrawing group. Activity by substituted piperazine at 2nd position of thiazole linked with quinazolinone scaffold gave better activity in the order of H > CH3 > CO–C6H5. Our findings may impart new direction to medicinal chemists and biochemists for further investigations of quinazolinone-thiazole containing anticancer agents.

A series of novel glutamine linked 2,3-disubstituted quinazolinone conjugates was synthesized from methyl anthranilate and different substituted acids and acid chlorides. The compounds 5a–l were prepared in good yields. All compounds were screened for their antibacterial activity against Gram-positive and Gram-negative bacteria and for antifungal activity against Candida albicans and Aspergillus flavus using paper disk diffusion technique. The minimum inhibitory concentrations of the compounds were also determined by agar streak dilution method. The compound 5b was found to exhibit the most potent in vitro anti-microbial activity. When tested for their antioxidant activity, compounds 5i and 5l showed potent radical scavenging activity, while compound 5g had moderate effect against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, nitric oxide, and superoxide radical scavenging assays. These results suggest that, the three quinazolinone analogs (5g, 5i, and 5l) could be considered as useful templates for future development to obtain more potent antioxidant agents.

4-(4-Oxo-4H-3,1-benzoxazin-2-yl)phenyl-4-methylbenzenesulfonate (2) was prepared and reacted with some primary aromatic amines, e.g., aniline, p-chloro aniline, p-methoxy aniline, p-amino benzoic acid and p-amino acetophenone. It reacted also with some heterocyclic amines, e.g., 2-aminothiazole, 2-aminobenzothiazole, 5-amino-4-phenylazo-2,4-dihydropyrazol-3-one and 3-amino-2-methylquinazolinone and with diamines; e.g., o-phenylenediamine, p-phenylenediamine, ethylenediamine, semicarbazide hydrochloride and thiosemicarbazide under different conditions. On the other hand, compound (2) reacted with both sodium azide and active methylene compounds, e.g., ethylcyanoacetate and ethylacetoacetate to give (19) and (20), respectively. All new prepared compounds were subjected to antimicrobial activity evaluation.

Some of new 3-(4-chlorophenyl or 4-fluorophenyl)-6-iodo-4-oxo-3,4-dihydroquinazoline derivatives having a Schiff bases, oxazolone, imidazolidine, pyrazolidine, pyridine, pyrimidine, and various substituted C-2 have been synthesized. Screening for some selected compounds was carried out for their potential anti-inflammatory and analgesic activity.

In this study, a novel series of quinazolinone derivatives analogue to nitraquazone structure were synthesized. The compounds tested for their inhibitory activity against phosphodiesterase 4B revealed that compound 6d shows promising inhibitory activity comparable to that of Rolipram, whereas compounds 6a and 6c exhibited moderate inhibitory activity.

A series of N-{5-[(2-chlorophenyl)methylene]-2-(4-hydroxyphenyl]-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamides (6a–n) have been synthesized. All the synthesized compounds were screened for in vitro antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger, and Aspergillus clavatus. The structures of the compounds were elucidated by IR, 1H NMR, 13C NMR, and Mass spectra.

3-(Aryl)-2-(2-chlorophenyl)-6-{2-[2-(2-chlorophenyl)-4-oxo(3-hydroquinazolin-3yl)]ethyl}-3-hydroquinazolin-4-ones had been selected as target bio-active molecules. Several quinazoline derivatives were prepared by using anthranilic acid, acid chloride, 2-amino-ethanol, and different amines. Newly synthesized compounds were screened for their antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger, and Aspergillus clavatus. The compounds 5e, 5g, and 5h are shown to have excellent activity, while 5c, 5d, 5i, 5k, 5l are shown to have very good activity against several strains of bacteria. The structures of the synthesized compounds were firmly established by well-defined spectral analysis techniques like IR, 1H-NMR, 13C-NMR, and Mass spectra.

A number of 2-substituted and 2,3-disubstituted quinazolinone analogues have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H NMR, and MS). An evaluation of the anticonvulsant activity of the prepared compounds has indicated that some of them exhibit moderate to significant activity, compared to diazepam and phenobarbital standards.

A new class of 2-azetidinyl-4-quinazolinones 6a–k was synthesized by multi-step process, starting from 2-[2-(2,6-dichlorophenyl)amino]phenyl acetic acid 1. Acid 1 was easily converted to acid chloride 2, which on cyclization reaction with 5-bromo anthranilic acid yielded benzoxazinone 3. The condensation reaction of 3 with benzene-1,4-diamine afforded 4-quinazolinone 4. Finally the title compound 6a–k was synthesized from 4-quinazolinone 4 by Schiff base formation 5a–k with aromatic aldehyde and then cyclization reaction with chloroacetylchloride. The in vitro antimicrobial activity of compounds 5a–k and 6a–k were tested. These compounds showed pronounced antimicrobial activity when 4-Cl and 4-OCH 3 groups were present.

A new series of 2-methyl-3H-quinazolinones substituted at the third position with amino acids (2–5) and aryl amine (6, 7) was designed, synthesized, and analyzed by infrared, NMR, and mass spectral analysis. Further, the compounds were screened for their in vivo antimalarial activity using the rodent malaria parasite Plasmodium yoelii (N-67) with the Swiss mice model. The compounds were also tested for their antibacterial activity.

Two series of 6,8-disubstituted-2-phenyl-3-(substituted benzothiazole-2-yl)-4[3H]-quinazolinone (1–13 and 14–26) were synthesized by reported method and evaluated for their phosphodiesterase inhibitory activity. All test compounds exhibited good activity. The structure–activity relationships based on the results obtained for these series were also studied. In both series, electron-withdrawing substitutions showed more activity. Among the tested compounds 6,8-dibromo-2-phenyl-3-(5-chloro benzothiazole-2-yl)-4[3H]-quinazolinone (20) and 6,8-dibromo-2-phenyl-3-(6-nitro benzothiazole-2-yl)-4[3H]-quinazolinone (24) were found to be even more potent than theophylline (IC50 of 1438 ± 85 μM for 20 and 1520 ± 48 μM for 24).

Several 3-[5-(4-substituted)phenyl-1,3,4-oxadiazole-2-yl]-2-styryl quinazoline-4(3H)-one were synthesized and screened for antibacterial activity against Staphylococcus aureus , Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli and antifungal activity against Aspergillus niger and Fusariumoxysporum by the serial dilution technique. Compounds were prepared by reacting corresponding 2-methtyl quinazolinone and 4-subustituted benzaldehydes in glacial acetic acid. Physicochemical and spectral data were consistent with newly synthesized compounds. The prepared compounds were compared with previously synthesized 2-methyl-3-[5-(4-substituted)phenyl-1,3,4-oxadiazole-2-yl]-quinazoline-4(3H)-ones for antimicrobial activity. The present study revealed that styryl moiety at the second position of 4(3H) quinazolinone marginally increased the biological activity and exhibited better antibacterial than antifungal activities.