Novel Oleanolic Acid-Phtalimidines Tethered 1,2,3 Triazole Hybrids as Promising Antibacterial Agents: Design, Synthesis, In Vitro Experiments and In Silico Docking Studies.

As part of the valorization of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3β-hydroxyolean-12-en-28-oic acid, )-phtalimidines (isoindolinones) conjugates - bearing 1,2,3-triazole moieties were designed and synthesized by treating an azide previously prepared from isolated from olive pomace ( L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. and its newly prepared analogues, - were screened in vitro for their antibacterial activity against two Gram-positive bacteria, and , and two Gram-negative bacteria, and .

Site-Selective Palladium(II)-Catalyzed Methylene C(sp)-H Diarylation of a Tropane Scaffold.

A series of 2,4-di-arylated tropane derivatives was synthesized through a site-selective palladium-catalyzed β-C(sp)-H di-arylation process. This type of structure has been scarcely reported in literature. They nevertheless represent an interesting class of biologically relevant molecules as illustrated by the observed activity at the micromolecular level of eight derivatives toward human colorectal cancer cell line HCT116.

Synthesis and In Silico Docking Study towards M-Pro of Novel Heterocyclic Compounds Derived from Pyrazolopyrimidinone as Putative SARS-CoV-2 Inhibitors.

In addition to vaccines, antiviral drugs are essential in order to suppress COVID-19. Although some inhibitor candidates have been determined to target the SARS-CoV-2 protein, there is still an urgent need to continue researching novel inhibitors of the SARS-CoV-2 main protease 'Omicron P132H', a protein that has recently been discovered. In the present study, in the search for therapeutic alternatives to treat COVID-19 and its recent variants, we conducted a structure-based virtual screening using docking studies for a new series of pyrazolo[3,4-]pyrimidin-4(5)-one derivatives -, which were synthesized from the condensation reaction of pyrazolopyrimidinone-hydrazide () with a series of electrophiles.

Design, Microwave-Assisted Synthesis and In Silico Prediction Study of Novel Isoxazole Linked Pyranopyrimidinone Conjugates as New Targets for Searching Potential Anti-SARS-CoV-2 Agents.

A series of novel naphthopyrano[2,3-]pyrimidin-11(12)-one containing isoxazole nucleus was synthesized under microwave irradiation and classical conditions in moderate to excellent yields upon 1,3-dipolar cycloaddition reaction using various arylnitrile oxides under copper(I) catalyst. A one-pot, three-component reaction, -propargylation and Dimroth rearrangement were used as the key steps for the preparation of the dipolarophiles. The structures of the synthesized compounds were established by H NMR, C NMR and HRMS-ES means.

Synthesis and Docking of New Pyrazolo[]pyrido[]pyrimidine-based Cytotoxic Agents.

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-]pyrido[1,2-]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV-Vis, H NMR, C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells.

Glioblastoma-specific anticancer activity of newly synthetized 3,5-disubstituted isoxazole and 1,4-disubstituted triazole-linked tyrosol conjugates.

Two series of 3,5-disubstituted isoxazoles (6a-e) and 1,4-disubstituted triazoles (8a-e) derivatives have been synthesized from tyrosol (1), a natural phenolic compound, detected in several natural sources such as olive oil, and well-known by its wide spectrum of biological activities. Copper-catalyzed microwave-assisted 1,3-dipolar cycloaddition reactions between tyrosol-alkyne derivative 2 and two series of aryl nitrile oxides (5a-e) and azides (7a-e) regiospecifically afforded 3,5-disubstituted isoxazoles (6a-e) and 1,4-triazole derivatives (8a-e), respectively in quantitative yields. Synthesized compounds were purified and characterized by spectroscopic means including 1D and 2D NMR techniques and HRMS analysis.

Synthesis, biological evaluation and molecular docking analysis of novel benzopyrimidinone derivatives as potential anti-tyrosinase agents.

2-substitued-benzopyrimidinones 2 were synthesized in high to excellent yields in a single step via condensation of 2-aminobenzamide 1 with some aryl-aldehydes in the presence of iodine. Cyclocondensation reaction of hydrazides 3 which were obtained in two steps from benzopyrimidinones 2, with some electrophilic species such as 2,4-pentandione, 2,5-hexandione, 1-phenylbutan-1,3-dione and cyclic anyhdrides provided the new compounds 4a-c, 5a-c, 6a-c, 7a-c, 8a-c and 9a-c. The synthesized compounds were characterized by spectroscopic means.

Design and synthesis of novel potent anticoagulant and anti-tyrosinase pyranopyrimidines and pyranotriazolopyrimidines: Insights from molecular docking and SAR analysis.

Pyrimidine-fused compounds are of great interest for the discovery of potent bioactive agents. This study describes the synthesis of novel pyranopyrimidines 3a-f and pyranotriazolopyrimidines 4a-d derivatives via the cyclocondensation reaction of α-functionalized iminoether 2, which was obtained from 2-amino-3-cyanopyrane 1, with a series of primary aromatic amines and hydrazides, respectively. Structures of all synthesized compounds were established on the basis of spectroscopic methods including H NMR, C NMR and ES-HRMS.

Synthesis of new anticancer and anti-inflammatory isoxazolines and aziridines from the natural (-)-deltoin.

Objectives: This work describes the synthesis, the bioactivity and the structure-activity relationship of new derivatives from a natural coumarin.

Methods: (-)-Deltoin 1 and the corresponding isoxazolines and aziridines were characterized by spectroscopic means. The cytotoxic (HTC-116, IGROV-1 and OVCAR-3 cancer cell lines) and 5-lipoxygenase activity of (-)-deltoin 1 and its structural analogues have been evaluated.

Synthesis and biological evaluation of novel pyrazolopyrimidines derivatives as anticancer and anti-5-lipoxygenase agents.

A novel series of 6-aryl-3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 3a-h were synthesized in a single step via condensation of carboxamide 2 with some aromatic aldehydes (presence of iodine). Treatment of aminopyrazole 1a with acetic anhydride afforded pyrazolopyrimidines 4 which on treatment with ethyl chloroacetate in refluxing dry DMF furnished a single product identified as ethyl 2-(3,6-dimethyl-4-oxo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl) acetate 5. On the other hand, esterification of compound 6 with different alcohol, led to the formation of new esters linked pyrazolo[3,4-d]pyrimidinones hybrids 7a-f.

Design and synthesis of antimicrobial, anticoagulant, and anticholinesterase hybrid molecules from 4-methylumbelliferone.

We designed and synthesized new series of diverse triazoles, isoxazoles, isoxazolines, and aziridines linked 4-methylumbelliferone 1 using intermolecular 1,3-dipolar cycloaddition reactions. Structures of these compounds were established on the basis of (1)H NMR, (13)C NMR, and ESI-HRMS. All prepared compounds were evaluated for their antimicrobial, anticoagulant, and anticholinesterase activities.

Design, synthesis of novel pyranotriazolopyrimidines and evaluation of their anti-soybean lipoxygenase, anti-xanthine oxidase, and cytotoxic activities.

The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes 2a-e has been accomplished by reaction of 2-acetonitrile derivatives 1a-e with hydroxylamine. Cyclocondensation reaction of precursors 2a-e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives 3a-e, 4a-e, and 5a-e, respectively. On the other hand, the reaction of precursors 2a-e with 2-chloropropanoyl chloride afforded the new acetimidamides 6a-e which evolve under reflux of toluene to the new oxadiazoles 7a-e.

Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities.

Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by (1)H NMR, (13)C NMR and HRMS.