Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum

Gellis, Armand; Primas, Nicolas; Hutter, Sébastien; Lanzada, Gilles; Remusat, Vincent; Verhaeghe, Pierre; Vanelle, Patrice; Azas, Nadine

doi:10.1016/j.ejmech.2016.04.059

Cited by 20 publications

(5 citation statements)

References 34 publications

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“…The search for novel antibacterial drugs is an attractive purpose for medicinal chemists [2]. Quinazolinone derivatives have shown biological activities including, anticancer [3], Antiepileptic [4], antiplasmodial [5], and antihistaminic activities [6]. Rezaee Nasab et al [7], reported quinazolinone derivatives as potential antibacterial agent.…”

Section: Introductionmentioning

confidence: 99%

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2022

J. Med. Chem. Sci.

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In this research, a new series of dihydroquinazolinone analogs (4a-f) was synthesized using a one-pot reaction supporting solvent-free conditions at the presence of SnCl2.2H2O as catalyst. All final products were proved by FT-IR, 1 H-NMR, and 13 C-NMR analysis. The preliminary antimicrobial activity was assessed against Gram-negative (Escherichia coli, Pseudomonas aeruginosa), Gram-positive (Staphylococcus aureus, Bacillus subtilis, Lactobacillus rhamnosus), and antifungal activities against Candida albicans. Most of the synthesized derivatives revealed considerable activity, significantly compounds 4d and 4e at 0.25 mg/mL concentration had the highest activity against P. aeruginosa. Also, the MIC of compound 4d was 0.25 mg/mL against B. subtilis, and L. rhamnosus. Furthermore, the tested molecules demonstrated moderate antifungal activities against the C. albicans.

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Section: Introductionmentioning

confidence: 99%

Untitled

2022

J. Med. Chem. Sci.

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“…In particular, they serve to block the synthesis of hepatitis C virus RNA, thus inhibiting the replication of the virus (Figure 2). In 2016, P. Verhaeghe, P. Vanelle, et al introduced 4-benzyloxy/4-amino and 2-trichloromethyl groups into the 1,3-quinazolines [6,7]. The resulting compounds as well as 2-amino analogs [8] may serve as inhibitors for histone (lysine) methyltransferase (HMT).…”

Section: Introductionmentioning

confidence: 99%

“…They may thus inhibit the mechanism of G9a during metastasis of cancer cells in vivo. Among 35 different analogs tested, those containing (chiral) 4-benzyl-oxy and -amino groups showed interesting anti-Plasmodium activities [6].…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Synthesis of Trifluoroethyl-Based, Chiral 3-Benzyloxy-1- and -2-Phenyl-quinazolinones of Biomedicinal Interest by Radical Type Cross-Coupling to Olefins

Chen

Chang

Tseng

et al. 2022

IJMS

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Several 2-substituted (H, Ph, and S-Me) and 1-substituted (H, Ph, and Bn), 3-hydroxy-1,3-quinazolin(di)ones were utilized for the first time as radical trapping agents in asymmetric 1,2-oxytrifluoromethylation of styrenes catalyzed by chiral vanadyl methoxide complexes bearing 3,5-disubstituted-N-salicylidene-t-leucinate templates. The effects of catalysts and solvents on the asymmetric induction were systematically examined. The best and complementary scenarios involved the use of vanadyl complexes V(O)-1 and V(O)-2, which bear 3-(2,5-dimethyl)phenyl-5-bromophenyl and 3-t-butyl-5-bromophenyl groups in an i-propanol solvent at ambient temperature. The corresponding (R)-cross-coupling products by V(O)-1 were obtained in 45–71% (for 2-substituted series) and 59–93% yields (for 1-substituted series) for p-/m-methylstyrenes and m-halo/CF3/CO2Me-styrenes in 38–63% ees (the best in 2-H case) and 60–84% ees (the best in 1-benzyl cases), respectively. The corresponding (S)-cross-coupling products by V(O)-2 were obtained in 28–55% (for 2-substituted series) and 45–72% yields (for 1-substituted series) for the same substrate class in 50–91% ees (85–91% ees in 2-phenyl cases) and 64–75% ees (up to 74–75% ees for each 1-H, Ph, and Bn cases), respectively. Theoretical calculations were carried out to explain the origin and extent of enantiocontrols. They both may serve as potential inhibitors of acetohydroxyacid synthase and epidermal growth factor receptor (EGFR) kinases.

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“…Introducing an oxygen atom as a linker between position four of the quinazoline moiety and the phenyl group led to a two-fold improvement in antiplasmodial activity for compound B ( Table 1 ) [ 10 ]. To study the Structure-Activity Relationships (SAR) related to the nature of the linker, an atom of carbon was added to provide a two-atom linker in 4-benzyloxy-2-trichloromethylquinazoline derivatives [ 11 ]. The resulting modification did not improve antiplasmodial activity, as shown with compound C ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antiplasmodial Evaluation of 4-Carboxamido- and 4-Alkoxy-2-Trichloromethyl Quinazolines

et al. 2020

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From three previously identified antiplasmodial hit compounds (A–C) and inactive series (D), all based on a 2-trichloromethylquinazoline scaffold, we conducted a structure-activity relationship (SAR) study at position four of the quinazoline ring by synthesizing 42 novel derivatives bearing either a carboxamido- or an alkoxy-group, to identify antiplasmodial compounds and to enrich the knowledge about the 2-trichloromethylquinazoline antiplasmodial pharmacophore. All compounds were evaluated in vitro for their cytotoxicity towards the HepG2 cell line and their activity against the multiresistant K1 P. falciparum strain, using doxorubicin, chloroquine and doxycycline as reference drugs. Four hit-compounds (EC50 K1 P. falciparum ≤ 2 µM and SI ≥ 20) were identified among 4-carboxamido derivatives (2, 9, 16, and 24) and two among 4-alkoxy derivatives (41 and 44). Regarding the two most potent molecules (16 and 41), five derivatives without a 2-CCl3 group were prepared, evaluated, and appeared totally inactive (EC50 > 50 µM), showing that the 2-trichloromethyl group was mandatory for the antiplasmodial activity.

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Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum

Cited by 20 publications

References 34 publications

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Asymmetric Synthesis of Trifluoroethyl-Based, Chiral 3-Benzyloxy-1- and -2-Phenyl-quinazolinones of Biomedicinal Interest by Radical Type Cross-Coupling to Olefins

Synthesis and Antiplasmodial Evaluation of 4-Carboxamido- and 4-Alkoxy-2-Trichloromethyl Quinazolines

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