Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt.
Published: May 2018
AI Article Synopsis
Article Abstract
Aim: Novel quinazolinone and triazinoquinazolinone derivatives were designed and synthesized as apoptotic inducers.
Methodology/results: Most of the synthesized compounds showed excellent antiproliferative activity against MCF-7 and HCT-116 cell lines, respectively. Compounds 7a, 8a, 8d, 14a and 14d were superior to doxorubicin as activators of caspases 3, 8 and 9 in HCT-116 cell line. The most potent caspase inducers, 8d and 14a showed cell cycle arrest mainly in G1 and S phase, respectively and increased the levels of p53, Bax and the Bax/Bcl-2 ratio compared with doxorubicin in HCT-116 cells with excellent selectivity against CCD-18Co human colon normal cell line.
Conclusion: The synthesized compounds can be considered as potent apoptotic inducers interfering with extrinsic and intrinsic apoptotic pathways.
Molecular editing of quinazolinones to isoquinolines by a novel ruthenium-catalyzed [4+2] annulation with sulfoxonium ylides has been developed. The method permits the precise and rapid assembly of multisubstituted aminoisoquinolines, a class of heterocycles that play a privileged role in organic synthesis and pharmaceutical development. This new catalytic process exhibits novel programmability, including directed C-H acetylation, nucleophilic cyclization, and alcoholysis.
Objective: Fruquintinib, a novel anti-angiogenic targeted drug, has gained widespread application in the treatment of metastatic colorectal cancer. This study aims to investigate the impact of the prognostic nutritional index (PNI) on the safety and survival outcomes of patients undergoing fruquintinib treatment for metastatic colorectal cancer.
Methods: A cohort of 106 patients with metastatic colorectal cancer, treated with fruquintinib at Zhejiang Cancer Hospital between 2019 and 2023, was included in this study.
In connection with previous work on V-shaped polycyclic thiazolo[5,4-]quinazolin-9-one and [5,4-]quinazoline derivatives that can modulate the activity of various kinases, the synthesis of straight thiazole-fused [4,5-] or [5,4-]quinazolin-8-ones and quinazoline derivatives hitherto undescribed was envisioned. An innovative protocol allowed to obtain the target structures. The synthesis of inverted thiazolo[4,5-] and [5,4-]quinazolin-8-one derivatives was also explored with the aim of comparing biological results.
Institute of Pharmaceutical Chemistry Albert Lespagnol (ICPAL), Faculty of Pharmacy, University of Lille, Rue du Professeur Laguesse, BP-83, F-59006 Lille, France; University of Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France; OncoWitan, Scientific Consulting Office, Wasquehal, F-59290 Lille, France. Electronic address:
Mackinazolinone is the main alkaloid isolated from plants of the genus Mackinlaya, essentially distributed in tropical Asia and Australia. There are five Mackinlaya species all containing bioactive alkaloids with a tetrahydropyridoquinazolinone core such as mackinazoline (1) and mackinazolinone (2). The present review retraces the origin of mackinazolinone and compares the different chemical routes to synthesize the natural product, through different methods including classical batch synthesis, solid-phase supported synthesis, microwaved irradiation and photochemistry.
Background: In response to the urgent need for continuous discovery of new anti-proliferative agents, a new series of quinazoline compounds was prepared.
Methods: As a reference, four cancer cell lines-HCT116, HePG2, Hela, and MCF-7-and sorafenib (SOR) were used to assess the novel motifs' in vitro anticancer efficacy. The most cytotoxic compounds were tested in a VEGFR-2 suppressive test and flow cytometric test.
