Synthesis, antimalarial activity, and target binding of dibenzazepine-tethered isoxazolines

Kumar, K.S. Vinay; Lingaraju, Gejjalagere S.; Bommegowda, Yadaganahalli K.; Vinayaka, A. C.; Bhat, Parvati; Kumara, C. S. Pradeepa; Rangappa, Kanchugarakoppal S.; Gowda, D. Channe; Sadashiva, M. P.

doi:10.1039/c5ra17926b

Cited by 19 publications

(20 citation statements)

References 37 publications

(48 reference statements)

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“…The yields of 47-49 are quite similar to certain compounds in [76], whereas for 50 (in analogy to the reaction with cyclopentene [76]), the yield is lower as expected. 4,5-Dihydroisoxazoles were found to exhibit potent cytotoxic, antineoplastic [77], and antimalarial activity [78]. Additionally, they can be used as androgenic or antiandrogenic agents or androgen receptor modulators [79] and show antibacterial and antifungal activities [80].…”

Section: 5-dihydroisoxazolesmentioning

confidence: 99%

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Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds

Zapol’skii

Bilitewski²,

Kupiec³

et al. 2020

Molecules

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Substituted nitrogen heterocycles are structural key units in many important pharmaceuticals. A new synthetic approach towards heterocyclic compounds displaying antibacterial activity against Staphylococcus aureus or cytotoxic activity has been developed. The selective synthesis of a series of 64 new N-heterocycles from the three nitrobutadienes 2-nitroperchloro-1,3-butadiene, 4-bromotetrachloro-2-nitro-1,3-butadiene and (Z)-1,1,4-trichloro-2,4-dinitrobuta-1,3-diene proved feasible. Their reactions with N-, O- and S-nucleophiles provide rapid access to push-pull substituted benzoxazolines, benzimidazolines, imidazolidines, thiazolidinones, pyrazoles, pyrimidines, pyridopyrimidines, benzoquinolines, isothiazoles, dihydroisoxazoles, and thiophenes with unique substitution patterns. Antibacterial activities of 64 synthesized compounds were examined. Additionally, seven compounds (thiazolidinone, nitropyrimidine, indole, pyridopyrimidine, and thiophene derivatives) exhibited a significant cytotoxicity with IC50-values from 1.05 to 20.1 µM. In conclusion, it was demonstrated that polyhalonitrobutadienes have an interesting potential as structural backbones for a variety of highly functionalized, pharmaceutically active heterocycles.

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Section: 5-dihydroisoxazolesmentioning

confidence: 99%

“…Dihydroisoxazoles were found to exhibit potent cytotoxic, antineoplastic [77], and antimalarial activity [78]. Additionally, they can be used as androgenic or antiandrogenic agents or androgen receptor modulators [79] and show antibacterial and antifungal activities [80].…”

Section: Molecules 2019 24 × For Peer Reviewmentioning

confidence: 99%

Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds

Zapol’skii

Bilitewski²,

Kupiec³

et al. 2020

Molecules

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show abstract

“…Each complex simulation box consists of 19,595–19,598 water molecules. The system simulation was run for 100 ns, during which 1000 structures were saved from the trajectory . To understand the stability of the protein‐ligand complex of 2 f ‐ 6 , the RMS deviations between the original structure and structures obtained from MD simulation were plotted.…”

Section: The Results and Discussionmentioning

confidence: 99%

“…[68] The synthesized molecules comparatively overcome and balance the (Log P o/w values, Log S values) lipophilicity, and solubility issues (Supplementary Information Table-1 (Table 1), efficiently satisfies few criteria for orally bioavailable molecule i. e. molecular weight < 500, Log P < 5.0. 53,69 Molecular dynamics simulations Molecular dynamics simulations were performed to test the stability of the predicted poses of most active molecules and the nature of the most stable interactions. MD simulations were run on the docked complex of biologically active molecules 2 f-6, 5 f-5.…”

Section: Structure-activity Relation Studiesmentioning

confidence: 99%

“…The system simulation was run for 100 ns, during which 1000 structures were saved from the trajectory. [44,69,70] To understand the stability of the proteinligand complex of 2 f-6, the RMS deviations between the original structure and structures obtained from MD simulation were plotted. The protein backbone did not show large deviation, and more consistent structural stability was observed after 20 ns frame.…”

Section: Structure-activity Relation Studiesmentioning

confidence: 99%

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Design and Synthesis of New Tubulin Polymerization Inhibitors Inspired from Combretastatin A‐4: An Anticancer Agent

et al. 2020

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A series of 30 small hybrid molecules are synthesized inspired from Combretastatin A-4 (CA-4), where ethylene-bridge of CA-4 is replaced with two five-membered heterocyclic rings, viz. isoxazoline and 1, 2, 3-triazole. These are joined by a methylene linker, with substitutions at A and Bring position of CA-4. The new molecular entities have shown significant cytotoxicity to cancer cell from the IC 50 0.49 μM-3.17 μM with 1-((4,5-Dihydro-3-(2,5-dimethoxyphenyl)isoxazol-5-yl)methyl)-4-(4-methoxyphenyl)-1H-1,2,3-triazole displayed IC 50 0.422 � 0.07 μM for A-549-lung cancer cell line and IC 50 0.498 � 0.03 μM for MDA-MB-231-breast cancer cell line. The western blot analysis, confocal staining and also by in vitro tubulin polymerization assay established the target specificity of the molecules as a tubulin polymerization inhibitor. Molecular docking & Molecular dynamics studies confirmed the binding interaction patterns of these molecules at the Colchicine binding site of tubulin and have correlated the observed experimental result with variation in structure satisfactorily.

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2‐Isoxazolines: A Synthetic and Medicinal Overview

Kumar

Shankar

2020

ChemMedChem

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Isoxazolines are nitrogen‐ and oxygen‐containing five‐membered heterocyclic scaffolds with extensive biological activities. This framework can be readily obtained in good to excellent yields through 1,3‐dipolar cycloaddition between nitrones with alkynes or allenes, aryl/alkyl halides, alkynes, and oxaziridines under mild conditions. This scaffold has been an emerging area of interest for many researchers given their wide range of bioactivities. Herein we review synthetic strategies toward isoxazolines and the role these efforts have had in enhancing the biological activity of natural products and synthetic compounds such as antitubercular agents, COX‐1 inhibitors, COX‐2 inhibitors (e. g., valdecoxib), nicotinic receptor modulators, and MIF inhibitors. With a focus on efforts from 2010 onward, this review provides in‐depth coverage of the design and biological evaluation of isoxazoline systems and their impact on various pathologies.

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Synthesis, antimalarial activity, and target binding of dibenzazepine-tethered isoxazolines

Abstract: A series of dibenzazepine tethered 3,5-disubstituted isoxazolines was synthesized and evaluated for their antimalarial activity usingP. falciparum3D7 strain. Further, the potent molecules were assessed againstP. falciparumD6, W2 and 7G8 strains.

Cited by 19 publications

References 37 publications

Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds

Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds

Design and Synthesis of New Tubulin Polymerization Inhibitors Inspired from Combretastatin A‐4: An Anticancer Agent

2‐Isoxazolines: A Synthetic and Medicinal Overview

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