Synthesis of New Proteomimetic Quinazolinone Alkaloids and Evaluation of Their Neuroprotective and Antitumor Effects

Abstract

New quinazolinone derivatives of the marine-derived alkaloids fiscalin B (3) and fumiquinazoline G (1), with neuroprotective and antitumor effects, were synthesized. Eleven quinazolinone-containing indole alkaloids were synthesized, proceeding the anti analogs via a one-pot method, and the syn analogs by the Mazurkiewicz-Ganesan approach. The neuroprotection capacity of these compounds on the rotenone-damage human neuroblastoma cell SH-SY5y was evaluated using the MTT assay. Compounds 1, 3, 5, and 7 showed more than 25% protection. The antitumor activity was investigated using the sulforhodamine B assay and some compounds were tested on the non-malignant MCF-12A cells. Fumiquinazoline G (1) was the most potent compound, with GI50 values lower than 20 µM. Compounds 5, 7, and 11 were more active in all tumor cell lines when compared to their enantiomers. Compounds 5, 7, 10, and 11 had very little effect in the viability of the non-malignant cells. Differences between enantiomeric pairs were also noted as being essential for these activities the S-configuration at C-4. These results reinforce the previously described activities of the fiscalin B (3) as substance P inhibitor and fumiquinazoline G (1) as antitumor agent showing potential as lead compounds for the development of drugs for treatment of neurodegenerative disorders and cancer, respectively.

A Simple Metal-Free Cyclization for the Synthesis of 4-Methylene-3-Substituted Quinazolinone and Quinazolinthione Derivatives: Experiment and Theory

“…Many 3,4-dihydroquinazolin-2(1 H )-one derivatives have been previously synthesized (Huang et al, 2008; Khan et al, 2014, 2015, 2016; Kshirsagar, 2015; Camacho et al, 2016; Maiden and Harrity, 2016; Awad et al, 2018; Zhang et al, 2018; Elkholy et al, 2019; Gatadi et al, 2019; Long et al, 2019; Wang et al, 2019). For example, Wang et al (2009) reported the synthesis of 4-alkyl-2(1H)-quinazolinones via the cyclization of 1-(2-alkynyl-phenyl)ureas catalyzed by TfOH and Saunthwal et al (2015) described a green and catalyst-free straightforward tandem synthesis of functionalized tetrahydroquinazolines from 2-aminophenylacrylate.…”

Synthesis of Novel Methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates and Antitumor Activity Evaluation: Studies In Vitro and In Ovo Grafts of Chick Chorioallantoic Membrane (CAM) with a Triple Negative Breast Cancer Cell Line

“…These media were supplemented with 5% FBS for the cell growth inhibition assay (SRB) or with 10% FBS for the remaining experiments. The non-tumorigenic cell line MCF-12A was cultured in RPMI 1640 medium supplemented with hEGF (human epidermal growth factor; 20 ng/μL), hydrocortisone (500 ng/μL), 5% FBS and 1% Penicillin-Streptomycin (Gibco), as previously described [ 30 ]. All the cell lines were maintained as adherent cell cultures and kept at 37 °C in a humidified incubator containing 5% of CO 2 .…”

Effects of β-glucosidase and α-rhamnosidase on the Contents of Flavonoids, Ginkgolides, and Aroma Components in Ginkgo Tea Drink

“…The experiment was done as mentioned before [41]. MTT solution (4 mg/mL in PBS) was added (20 μL/well) into each well and incubated with cells for 4 h at 37 °C.…”