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Quinoxaline is a fused heterocycle system of a benzene ring and pyrazine ring. It has earned considerable attention due to its importance in the field of medicinal chemistry. The system is of extensive importance due to its comprehensive array of biological activities. Quinoxaline derivatives have been used as anticancer, anticonvulsant, anti-inflammatory, antidiabetic, antioxidant, antibacterial, anti-TB, antimalarial, antiviral, anti-HIV, and many other uses. Variously substituted quinoxalines are significant therapeutic agents in the pharmaceutical industry. This review spotlights on the chemistry, physiochemical characters, synthesis, pharmaceutical products, and medicinal chemistry of various anticancer quinoxaline derivatives that were developed in the last period. It covers the period from 2016 to 2023. [ABSTRACT FROM AUTHOR]

Cancer is a large group of diseases that can affect any organ or body tissue due to the abnormal cellular growth with the unknown reasons. Many of the existing chemotherapeutic agents are highly toxic with a low level of selectivity. Additionally, they lead to development of therapeutic resistance. Hence, the development of targeted chemotherapeutic agents with low side effects and high selectivity is required for cancer treatment. Quinazoline is a vital scaffold well-known to be linked with several biological activities. The anticancer activity is one of the prominent biological activities of this scaffold. Several established anticancer quinazolines work by different mechanisms on the various molecular targets. The aim of this review is to present different features of medicinal chemistry as drug design, structure activity relationship, and mode of action of some targeted anticancer quinazoline derivatives. It gives comprehensive attention on the chemotherapeutic activity of quinazolines in the viewpoint of drug discovery and its development. This review provides panoramic view to the medicinal chemists for supporting their efforts to design and synthesize novel quinazolines as targeted chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Quinazoline is an essential scaffold, known to be linked with various biological activities. Some of the prominent biological activities of this system are analgesic, anti-inflammatory, anti-hypertensive, anti-bacterial, anti-diabetic, anti-malarial, sedative–hypnotic, anti-histaminic, anti-cancer, anti-convulsant, anti-tubercular, and anti-viral activities. This diversity in the pharmacological response of the quinazoline system has encouraged medicinal chemists to study and discover this system and its multitude of potential against several biological activities. Many of these studies have successfully investigated the structure–activity relationship to explore the specific structural features of their biological targets. The developing understanding of quinazoline derivatives and their biological targets presents opportunities for the discovery of novel therapeutics. This review represents different aspects of medicinal chemistry, including drug design, structure–activity relationship, and the mode of action of some analgesic and anti-inflammatory quinazoline compounds. It pays comprehensive attention to the analgesic and anti-inflammatory activities of quinazolines from the viewpoint of drug discovery and its development. [ABSTRACT FROM AUTHOR]

New quinazoline-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds VI-6-a, V, IV-4, VI-4-c, IV-6, VI-2-a, IV-1, and IV-2 were more potent than the reference glibenclamide. They induced significant reduction in the blood glucose levels of diabetic rats: 78.2, 73.9, 71.4, 67.3, 62, 60.7, 58.4, and 55.9%, respectively, while the reference glibenclamide had 55.4%. Compounds IV-1, VI-2-a, IV-2, V, and IV-6 showed more prolonged antidiabetic activity than glibenclamide. Moreover, molecular docking and pharmacokinetic studies were performed to examine binding modes of the prepared compounds against peroxisome proliferator-activated receptor gamma (PPARγ). The highest active compounds exhibited good binding affinity with high free energy of binding against PPARγ. In silico absorption, distribution, metabolism, elimination and toxicity (ADMET) studies were performed to investigate pharmacokinetics and safety of the synthesized compounds. They showed considerable human intestinal absorption with low toxicity profile. [ABSTRACT FROM AUTHOR]

Photocatalytic hydrogen production has gained considerable attention as a sustainable method for renewable energy production. Lead sulfide (PbS) compound has significant reserves and a suitable bandgap for the production of hydrogen gas via the water photo-splitting process. However, the charge recombination effect of the charge carriers severely limits their potential use in solar water splitting. Herein, the photoelectrodes of PbS were fabricated through the chemical bath deposition method and then doped with different Mo concentrations to optimize the hydrogen photo-production activity. Both structural and performance characterizations of the photoelectrodes have been carried out using various characterization techniques. The photoelectrochemical (PEC) performance of molybdenum (Mo)-doped PbS photoelectrodes exhibits a significant increase in the photocurrent density with the optimum photocurrent density of 1.2 mA/cm2 obtained at 0.8 % Mo doping atomic ratio which was twelve times higher than that of a pure PbS photoelectrode. The doping of Mo induces the electron-hole separation yield which results in improved electron transport characteristics. The Mo doping was as act as a donor site that increased the PbS film conductivity. The newly optimized Mo–PbS was used as a promising photoelectrode supported on commercial glass using the optimum Mo-doped PbS photoelectrode, the photoelectrochemical (PEC) hydrogen production rate was reached 122 μmol/h cm2 during the solar water splitting process and the conversion efficiency of the incident photon-to-current (IPCE) value was 7.0 % at 390 nm monochromatic exposure. Moreover, the stability of the optimum electrode was evaluated as a function of the number of runs and exposure time in addition to the electrochemical impedance study. • (Mo)-doped PbS photoelectrodes (PbS) achieved significant increase in the photocurrent density for the production of hydrogen. • (PEC) hydrogen production rate exhibited 122 µmol/h cm2 during the solar water splitting process. • The conversion efficiency of the incident photon-to-current (IPCE) value was 7.0 % at 390 nm. • The stability of the optimum electrode was evaluated as a function of the number of runs and exposure time. [ABSTRACT FROM AUTHOR]

Abstract Some fluoroquinazolinones (A–H) were designed, synthesized and biologically evaluated for their antitumor activity against the two cell lines, MCF-7 and MDA-MBA-231. New derivative G (IC50 = 0.44 ± 0.01 µM) showed antitumor activity, better than that of the reference drug erlotinib (IC50 = 1.14 ± 0.04 µM) against MCF-7. New derivative E (IC50 = 0.43 ± 0.02 µM) showed higher activity than the reference drug erlotinib (IC50 = 2.55 ± 0.19 µM) against MDA-MBA-231. Furthermore, the EGFR (epidermal growth factor receptor) and tubulin inhibition assays were carried out for the highest active derivatives to reveal the expected mechanism of action. They exhibited significant results compared to the reference drugs. Molecular docking simulations were performed on EGFR and tubulin binding sites to rationalize the experimental results and describe their binding modes. The results of the molecular modeling study were correlated with that of the antitumor screening. [ABSTRACT FROM AUTHOR]

Some novel fluorinated quinazolines (5a-j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), 13C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization. [ABSTRACT FROM AUTHOR]

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Abstract: Objectives: The aim of the present work was to synthesize some novel fluorinated quinazolinones and to evaluate them for anticonvulsant activity and neurotoxicity. Methods: Eight compounds were synthesized. Their anticonvulsant activity was evaluated from maximal electroshock-induced seizures in eight groups of six Swiss mice given the test compounds (100mg/kg intraperitoneally), one control group given 10% DMSO (10ml/kg) and one given the reference compound phenytoin (100mg/kg). Neurotoxicity was evaluated by the rotarod test in eight groups of four Swiss mice given the test compounds (100mg/kg), one given saline (10ml/kg) and one given phenytoin (100mg/kg). The structure–activity relations of the compounds and ClogP correlations were determined to explain the results. Results: Four compounds showed significant anticonvulsant activity with low neurotoxicity when compared with the reference drug. Conclusion: The newly designed compounds could be useful templates for the design and optimization of more active analogues as anticonvulsant agents with low neurotoxicity. [Copyright &y& Elsevier]

Abstract: Some novel 6,8-diiodo-2-methyl-3-substituted-quinazolin-4(3H)-ones bearing sulfonamide derivatives (4–11) were synthesized in good yields and evaluated for their possible antibacterial, anti-inflammatory activities and acute toxicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Their antibacterial activities were evaluated by the agar well diffusion method while their anti-inflammatory activities were evaluated by the carrageenan-induced hind paw edema test. All the tested compounds showed considerable antibacterial activities and high to moderate anti-inflammatory activities that last for 12h compared to ibuprofen. All the tested compounds showed no toxic symptoms or mortality rates 24h post-administration at tested anti-inflammatory doses. In addition, LD50 for all tested compounds was higher than that for ibuprofen implying their good safety margin. The obtained results showed that the most active compounds could be useful as a template for future design, modification and investigation to produce more active analogs. [Copyright &y& Elsevier]