- Synthesis, in vitro, and in silico studies of newly functionalized quinazolinone analogs for the identification of potent α-glucosidase inhibitors
-
Functionalized quinazolinone derivatives 1–30 were synthesized by two-step reaction. First, anthranilic acid was treated with substituted phenyl isothiocyanate to synthesize 3-aryl-2-thioxo-2,3-dihydroquinazolinone derivatives 1–8 which in turn reacted with different bromoacetophenone derivatives to obtain fully functionalized quinazolinone derivatives 9–30. Both reactions were catalyzed by triethylamine. All the products were characterized by EI-, HREI-MS, 1H-, and 13CNMR spectroscopic techniques. All compounds were subjected to their in vitro α-glucosidase inhibitory activity. Results showed that except compound 1–3, 5, 7, and 22, all compounds were found potent and showed many folds increased α-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 ± 10.0?μM). Compound 13 (IC50 = 85.0 ± 0.5?μM) was recognized as the most potent analog of the whole series, with ninefold enhanced inhibitory potential than the standard acarbose. Compounds 1–9, 11, 12, 22, and 26 were structurally known compounds, while remaining all are new. Kinetic study on compound 13 showed that the compound is following a competitive-type inhibition mechanism. Furthermore, in silico studies have also been performed to better rationalize the interactions between synthetic compound and active site of the enzyme. Graphic abstract: [Figure not available: see fulltext.]
- Wali, Hayat,Anwar, Ayaz,Shamim, Shahbaz,Khan, Khalid Mohammed,Mahdavi, Mohammad,Salar, Uzma,Larijani, Bagher,Perveen, Shahnaz,Taha, Muhammad,Faramarzi, Mohammad Ali
-
p. 2017 - 2034
(2021/01/26)
-
- Synthesis, biological evaluation and molecular docking studies of novel quinazolinones as antitubercular and antimicrobial agents
-
In the present study, a series of novel quinazolinone hybrids, viz. triazepino-quinazolinones 4, thiazolo-triazolo-quinazolinones 7 and triazolo-quinazolinones 8 have been synthesized from the key intermediate 3-(substituted phenyl)-2-hydrazinoquinazolin-4(3H)-ones 3. All the newly synthesized compounds were characterized by means of spectral (IR, 1H NMR, 13C NMR) and elemental analysis. The target compounds were biologically screened for their in vitro antimicrobial and antitubercular activities against pathogenic strain. The results of bioassay demonstrated that some of the compounds exhibited pronounced antimicrobial activity comparable to that of standard drugs tested under similar conditions. Compounds 4c, 4e, 7e and 8b showed relatively very good inhibitory activity against pathogenic bacteria with minimum inhibitory concentration (MIC) of 2.6 μg/mL, 5.2 μg/mL, while the rest of the compounds showed moderate activity. Compounds 4c and 8b were found to be nearly equipotent with ciprofloxacin against P. aeruginosa with MIC 5.2 μg/mL, while compound 8b was more potent against pathogenic bacteria S. aureus. It is very remarkable that four compounds, 4c, 4e, 7e and 8b showed pronounced antifungal activity against selected pathogenic fungi, A. niger, C. albicans with MIC 2.6 μg/mL and 5.2 μg/mL. The antitubercular activity of synthesized compounds reveal that compound 8b showed better activity than the other compounds with a MIC of 5.2 μg/mL against M. tuberculosis (H37Rv). Molecular docking studies of the compounds were performed to rationalize the inhibitory properties of these compounds and results showed that these compounds have good binding energy and better binding affinity within the active pocket, thus these compounds may be considered as potent inhibitors towards selective targets.
- Kumar Pandey, Sarvesh,Yadava, Umesh,Upadhyay, Anjali,Sharma
-
-
- Identification of potent cholecystokinin-B receptor antagonists: Synthesis, molecular modeling and anti-cancer activity against pancreatic cancer cells
-
Advanced malignant stages of pancreatic cancer have poor prognosis and very few treatment strategies are available. Pancreatic cancer is known to possess unique growth-related receptors that when activated, stimulate tumour proliferation. Gastrin and its related peptide cholecystokinin (CCK) are also significantly involved in the growth of this cancer type as well as other malignancies through activation of the cholecystokinin-B receptor (CCK-BR). New treatment strategies with CCK-BR antagonists are being suggested that suppress the growth promoting effects of gastrin. In this paper, we report the development of two series of quinazolinone derivatives incorporating hydrazinecarbothioamide (compounds 3a-g) and the hydrazino group (compounds 4a-e) as linkers for developing CCK-BR antagonists. The affinities of the compounds were determined using docking into the CCK-BR homology modeled structure. The compounds were tested for in vitro CCK-BR binding and gastric acid secretion in an isolated lumen-perfused mouse stomach assay. The compounds exhibited CCK-BR binding activity (IC50) in the range of 0.2-975 nM and showed good gastric acid secretion inhibitory activity. Molecular modeling of the compounds was done and pharmacophore mapping results showed good prediction of in vitro activity which correlated well with the experimental antagonistic activity. The compounds were further tested for their cytotoxicity on CCK-BR expressing pancreatic cancer cells. The results of the study provided two potent CCK-BR antagonists which also possess good to moderate growth inhibitory activities against pancreatic cancer cells.
- Kumari, Saroj,Chowdhury, Joyita,Sikka, Manisha,Verma, Priyanka,Jha, Prakash,Mishra, Anil K.,Saluja, Daman,Chopra, Madhu
-
p. 1561 - 1574
(2017/07/25)
-
- A convenient and efficient synthesis of 2-thioxoquinazolinone derivatives via microwave irradiation
-
The synthesis of 2-thioxoquinazolinone derivatives was achieved by condensation of isatoic anhydride, primary amine, and carbon disulfide under microwave irradiation. This convenient and efficient method affords the desired products with good to excellent yields. Satisfactory infrared spectroscopy, 1H NMR, and high-resolution mass spectrometry (electrospray ionization) spectra were obtained for all compounds described.
- Liu, Weiwei,Zhang, Qiang,Gong, Feng,Cao, Zhiling,Huo, Yunfeng
-
p. 317 - 321
(2015/03/30)
-
- Some reactions with p-ethoxyphenylcyano-thioforamide: Synthesis of pyrrole, pyrrolo[2,3-c]pyrrole, imidazo[4,5-b]quinoxalines and hydantoin derivatives
-
P-Ethoxyphenylcyanothioformamide (1) was reacted with αβ-unsaturated ketone (2) and N-p-chlorophenylmaleimide (4) to furnish pyrrole and pyrrolo[2,3-c]pyrrol-4,6-diones (3) and (5) respectively. Also, interaction of 1 with anthranilic acid and o-phenylenediamine produced 3-(4′-ethoxyphenyl)-2-thioxoquinazolin-4-one (6) and 2-thioxobenzimidazoles (7). When, 1 was reacted with iso(thio)cyanates caused cyclization to afford 5-imino-4-thioxoimidazolidinones (9). Compound 9 was subjected to some reagents such as hydrazine hydrate, thiosemicarbazide, o-phenylenediamines, hydrogen sulfide and HCl to give 5-hydrazono, 4-thiosemicarbazono, and thiohydantoin derivatives (10-17), respectively.
- Ammar,El-Sharief,Ali,Mohamed,Mohamed
-
p. 173 - 185
(2007/10/03)
-
- Synthesis and Antibacterial Activity of 2-thio>-3-aryl(or alkyl)-6,8-disubstituted-4(3H)-quinazolinones
-
Synthesis of 47 new 2-thio>-3-aryl(or alkyl)-6,8-disubstituted-4(3H)-quinazolinones, 2-6, from the corresponding 2-thio-4(3H)-quinazolinones, 1, has been described.Fifteen of them were screened for their antibacterial activity by t
- Lakhan, Ram,Rai, Babban J.
-
p. 384 - 386
(2007/10/02)
-
- Copper(II) Complexes of 3-N-Aryl Substitute Thioquinazolones
-
CuII complexes and their pyridine adducts of 3-phenyl/p-tolyl/p-methoxyphenyl/p-ethoxyphenyl/p-chlorophenyl/p-bromophenyl-quinazoline-2-thione-4-one (HL) are prepared.Elemental analysis, magnetic and spectral data show that the copper complexes without pyridine have square-planar structure and the pyridine adducts have tetragonal structure.
- Dave, L. D.,Mathew, Cherian,Oommen, Varughese
-
p. 273 - 275
(2007/10/02)
-
