63586-34-5Relevant articles and documents
Synthesis and Pharmacological Evaluation of 3-propyl-2-substitutedamino-3H-quinazolin-4-ones as Analgesic and Anti-Inflammatory Agents
Sheorey,Thangathiruppathy,Alagarsamy
, p. 1371 - 1377 (2016)
A variety of novel 3-propyl-2-substitutedamino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-propyl quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-propyl quinazolin-4(3H)-one was synthesized from propylamine. The title compounds were investigated for analgesic and anti-inflammatory activities. The compound 2-(1-ethylpropylidene-hydrazino)-3-propyl-quinazolin-4(3H)-one (SR2) emerged as the most active compound of the series, and it is more potent in its analgesic and anti-inflammatory activities when compared with the reference standard diclofenac sodium.
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.
Identification of a New Heterocyclic Scaffold for Inhibitors of the Polo-Box Domain of Polo-like Kinase 1
Alverez, Celeste N.,Park, Jung-Eun,Toti, Kiran S.,Xia, Yangliu,Krausz, Kristopher W.,Rai, Ganesha,Bang, Jeong K.,Gonzalez, Frank J.,Jacobson, Kenneth A.,Lee, Kyung S.
, p. 14087 - 14117 (2020/11/30)
As a mitotic-specific target widely deregulated in various human cancers, polo-like kinase 1 (Plk1) has been extensively explored for anticancer activity and drug discovery. Although multiple catalytic domain inhibitors were tested in preclinical and clinical studies, their efficacies are limited by dose-limiting cytotoxicity, mainly from off-target cross reactivity. The C-terminal noncatalytic polo-box domain (PBD) of Plk1 has emerged as an attractive target for generating new protein-protein interaction inhibitors. Here, we identified a 1-thioxo-2,4-dihydro-[1,2,4]triazolo[4,3-a]quinazolin-5(1H)-one scaffold that efficiently inhibits Plk1 PBD but not its related Plk2 and Plk3 PBDs. Structure-activity relationship studies led to multiple inhibitors having ≥10-fold higher inhibitory activity than the previously characterized Plk1 PBD-specific phosphopeptide, PLHSpT (Kd ～450 nM). In addition, S-methyl prodrugs effectively inhibited mitotic progression and cell proliferation and their metabolic stability was determined. These data describe a novel class of small-molecule inhibitors that offer a promising avenue for future drug discovery against Plk1-addicted cancers.
