1031-88-5Relevant articles and documents
Discovery of Novel Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists as Regulators of Chondrogenic Differentiation: Identification of Quinazolin-4(3 H)-ones and in Vivo Studies on a Surgically Induced Rat Model of Osteoarthritis
Atobe, Masakazu,Nagami, Takamichi,Muramatsu, Shuji,Ohno, Takeshi,Kitagawa, Masayuki,Suzuki, Hiroko,Ishiguro, Masashi,Watanabe, Atsushi,Kawanishi, Masashi
, p. 1468 - 1483 (2019)
Osteoarthritis (OA) is a degenerative disease characterized by joint destruction and loss of cartilage. There are many unmet needs in the treatment of OA and there are few promising candidates for disease-modifying OA drugs, particularly, anabolic agents. Here, we describe the identification of novel quinazolin-4(3H)-one derivatives, which stimulate chondrocyte cartilage matrix production via TRPV4 and mitigate damaged articular cartilage. We successfully identified the water-soluble, highly potent quinazolin-4(3H)-one derivative 36 and studied its intra-articular physicochemical profile to use in in vivo surgical OA model studies. Compound 36·HCl provided relief from OA damage in a rat medial meniscal tear (MT) model. Specifically, 36·HCl dose-dependently suppressed cartilage degradation and enhanced the messenger RNA expression of aggrecan and SOX9 in cartilage isolated from MT-operated rat knees compared with knees treated with vehicle. These results suggest that 36 induces anabolic changes in articular cartilage and consequently reduces OA progression.
Design and synthesis of new benzylidene-quinazolinone hybrids as potential anti-diabetic agents: In vitro α-glucosidase inhibition, and docking studies
Ayyad, Rezk R.,Ibrahim, Albaraa,Khalifa, Mohamed M.,Mansour, Ahmed M.,Sakr, Helmy M.
, (2021/11/08)
A novel series of benzylidene-quinazolinone hybrids 8a,b and 10a-n were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory effect aiming to discover efficient anti-diabetic agents. The synthesized compounds were assessed for their in vivo anti-hyperglycemic activities against STZ-induced hyperglycemic rats. Five compounds (10m, 10f, 10c, 10d and 8b) demonstrated potent activities with percent reduction in blood glucose levels of 43.07, 40.14, 39.83, 37.04 and 36.16, respectively. The most active members were further evaluated in vitro for their α-glucosidase inhibitory binding affinities. Among them, Compound 10m containing 4-hydroxybenzylidene moiety and compound 10f with 4-chlorobenzylidene moiety connected to the acetohydrazide demonstrated the most potent inhibitory activities towards α-glucosidase with IC50 values of 561 and 610 μM, respectively. Molecular docking study was performed in order to understand the molecular interactions between the molecule and enzyme.
The natural-based optimization of kojic acid conjugated to different thio-quinazolinones as potential anti-melanogenesis agents with tyrosinase inhibitory activity
Sepehri, Nima,Iraji, Aida,Yavari, Ali,Asgari, Mohammad Sadegh,Zamani, Saeed,Hosseini, Samanesadat,Bahadorikhalili, Saeed,Pirhadi, Somayeh,Larijani, Bagher,Khoshneviszadeh, Mahsima,Hamedifar, Halleh,Mahdavi, Mohammad,Khoshneviszadeh, Mehdi
, (2021/03/01)
Melanin pigment and melanogenesis are a two-edged sword. Melanin has a radioprotection role while melanogenesis has undesirable effects. Targeting the melanogenesis pathway, a series of kojyl thioether conjugated to different quinazolinone derivatives were designed, synthesized, and evaluated for their inhibitory activity against mushroom tyrosinase. All the synthesized compounds were screened for their anti-tyrosinase activity and all derivatives displayed better potency than kojic acid as the positive control. In this regard, 5j and 5h as the most active compounds showed an IC50 value of 0.46 and 0.50 μM, respectively. In kinetic evaluation against tyrosinase, 5j depicted an uncompetitive inhibition pattern. Designed compounds also exhibited mild antioxidant capacity. Moreover, 5j and 5h achieved good potency against the B16F10 cell line to reduce the melanin content, whilst showing limited toxicity against malignant cells. The proposed binding mode of new inhibitors evaluated through molecular docking was consistent with the results of structure–activity relationship analysis.
Design, synthesis, in vitro and in silico biological assays of new quinazolinone-2-thio-metronidazole derivatives
Ansari, Samira,Asgari, Mohammad Sadegh,Biglar, Mahmood,Esfahani, Ensieh Nasli,Hamedifar, Haleh,Larijani, Bagher,Mahdavi, Mohammad,Mohammadi-Khanaposhtani, Maryam,Rastegar, Hossein,Tas, Recep,Taslimi, Parham
, (2021/07/08)
A new series of quinazolinone-2-thio-metronidazole derivatives 9a-o was designed, synthesized and assayed for their activities against metabolic enzymes human carbonic anhydrase I and II (hCAs I and II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against CA enzymes, 4-fluorophenyl derivative 9i, was 4 and 7-times more potent than standard inhibitor acetazolamide against hCA I and II, respectively; 4-fluorobenzyl derivative 9m as the most potent compound against cholinesterase enzymes, was around 11 and 21-times more potent than standard inhibitor tacrine against AChE and BChE, respectively; the most active α-glucosidase inhibitor 9h with 4-methoxyphenyl moiety was 5-times more active that acarbose as standard inhibitor. Furthermore, in order to study interaction modes of the most potent compounds in the active site of their related enzymes, molecular modeling was performed. Druglikeness, ADME, and toxicity profile of the compounds 9i, 9m, and 9h were also predicted.
