Synthesis of new 3,4-dihydropyrano[c]chromene derivatives and their evaluation as acetyl cholinesterase inhibitors

2-Amino-4-phenyl-4,5-dihydro-5-oxopyrano[2,3-c]chromen-3-carbonitrile derivatives (8a-d) have been isolated in good yields by the reaction of corresponding 4-hydroxycoumarin (1) with substituted aldehydes (2a-d) and malononitrile (3) under reflux conditions. The reactivity of α-functionalized iminoethers (9a-d) with hydrazine, hydroxylamine and piperidine was studied. The synthesized compounds were characterized by various techniques including spectroscopy. Compounds 8-11 were also evaluated as potential acetylcholinesterase inhibitors

Novel antimicrobial and anti-acetylcholinesterase dihydroisoxazoles from (R)-limonene

We report herein the convenient procedures for the efficient and easy synthesis, and the antimicrobial and the anti-acetylcholinesterase evaluation of two new series of (R)-limonene derivatives. A substantial modification aimed at targeting to discover novel structures with a better antimicrobial and anti-acetylcholinesterase (anti-AChE) activities. The condensation of (R)-limonene (1) with various arylnitrile oxides led, via the 1,3-dipolar cycloaddition reaction, conducted with complete region-specificity, to a series of new limonene-dihydroisoxazoles, 2a-h. On the other hand, N-alkylation of the previously prepared limonene-lactam derivative (3) yielded the corresponding dipolarophile (4), which affords by condensation with arylnitrile oxides the expected new dihydroisoxazoles, 5a-h. The target compounds were completely characterized by 1H NMR, 13C NMR and MS. All the synthesized heterocyclic compounds were tested for their antimicrobial and anti-acetylcholinesterase activities. The dihydroisoxazoles 2a (IZ = 13.25 mm, cc = 1 mg/mL) and 5b (IZ = 13.75 mm, cc = 1 mg/mL) exhibited the highest antifungal activity. The greatest anti-acetylcolinesterase activity was exhibited by 2f (IC50 = 82±3 µg/mL) and by 5a (IC50 = 99±1 µg/mL)

Sur l’identification de l’oppidum liberum Abziritanum et de l’ecclesia Auziritana à Ouzra, dans la région d’Oudhna-Mornag (Tunisie)

Many ancient literary sources, both classic and late antique, inform us about an oppidum liberum Abziritanum, the toponym Abdera and the ecclesia Auzritana. Our approach to this topic of study began by establishing a connection with the site of Ouzra, located a few kilometers north-east of Oudhna (ancient Uthina). Later, an investigation in the archives of the Carte Archéologique de Tunisie allowed us to find and exploit an archaeological documentation including a Latin inscription with the sentence Abzira libera and thus confirming its location in Hr Ouzra. The study of the whole epigraphic and literary documentation let us trace some moments of the history of Abzira during a period that goes from the I to the VII century AD.Plusieurs mentions littéraires anciennes, classiques et tardives, nous font connaitre un oppidum liberum Abziritanum, le toponyme Abdera et l’ecclesia Auzritana. Notre démarche dans la présente étude a commencé par un rapprochement avec le site d’Ouzra, situé à quelques kilomètres au nord-est d’Oudhna (l’antique Uthina). Ensuite, une enquête dans les archives de la Carte Archéologique de Tunisie nous a permis de retrouver et d’exploiter une documentation archéologique dont une inscription latine donnant la leçon Abzira libera et confirmant sa localisation à Hr Ouzra. L’étude de l’ensemble de la documentation épigraphique et littéraire nous a conduits à retracer quelques moments de l’histoire d’Abzira sur une période allant du Ier siècle au VIIe siècle

Erythema Nodosum Revealing Metastatic Lung Cancer

Erythema nodosum (EN) is an inflammatory condition of the subcutaneous fat and has been reported in patients with haematological malignancies (lymphomas) or solid tumours. Lung cancer is the most common cause of paraneoplastic syndrome. We report a case of EN occurring as a paraneoplastic disease.A 48-year-old Tunisian woman, a non-smoker with no relevant medical history, presented with painful, erythematous, firm nodules on her legs with ankle swelling. The patient did not report any other symptoms. There were no abnormalities on examination except for moderate fever. An extensive infectious and immunological investigation was negative. Antistreptolysin antibodies were undetectable. Chest radiography showed a focal opacity in the right lung and a CT scan revealed a mass in the lower right pulmonary lobe with hilar and mediastinal lymphadenopathies, a nodule in the right adrenal gland, condensation in the iliac bone and multiple bilateral nodular cerebral expansive processes. Bronchial biopsies revealed a primitive and moderately differentiated adenocarcinoma. No argument for tuberculosis or sarcoidosis was foun

Palladium-Catalysed Direct Arylations of Heteroaromatics bearing Dicyanovinyls at C2

International audienceThe palladium-catalysed direct 5-arylation of heteroaromatics bearing dicyanovinyls at C2 with aryl bromides via C-H bond functionalisation allows the synthesis of a variety of new conjugated systems in only one step. The nature of the solvent was found to be crucial to perform such arylations. In DMAc, complete decomposition of the dicyanovinyl derivatives was observed, whereas they were found to be stable in cyclopentyl methyl ether

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

International audience2-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. They were also evaluated for their anti-tyrosinase potential. The structure-activity relationship (SAR) was discussed on the basis of the molecular docking analysis. © 201

Synthesis of Novel Fused Coumarine and naphtho[2,1-b]pyrano[3,2- e][1,2,4] triazolo[1,5-c]pyrimidine Derivatives

International audienc

A Lobularia maritima LmSAP protein modulates gibberellic acid homeostasis via its A20 domain under abiotic stress conditions.

Stress-associated proteins (SAPs) are favorable targets to improve stress tolerance in plants, owing to their roles in developmental processes and stress responses. However, the role of SAPs and the molecular mechanisms by which they regulate plant stress responses remain poorly understood. Previously, it was reported that LmSAP expression was upregulated by various abiotic stressors in Lobularia maritima, and that transgenic tobacco lines with constitutively expressed LmSAPΔA20 and LmSAPΔA20-ΔAN1 showed dwarf phenotypes due to the deficiency of cell elongation under salt and osmotic stresses. In this study, we examined the function of A20 domain in the GA pathway in response to abiotic stresses. Transient expression of acGFP-LmSAPΔA20 and acGFP-LmSAPΔA20-ΔAN1 in onion epidermal cells demonstrated that these fused proteins were localized in the nucleo-cytoplasm. However, the truncated form acGFP-LmSAPΔAN1 was localized in the nucleus. Moreover, comparison of native and truncated LmSAP showed dramatic structural changes caused by the deletion of the A20 domain, leading to loss of function and localization. Interestingly, overexpression LmSAP and truncated LmSAPΔAN1 led to up-regulation of GA biosynthetic genes and increased total gibberellins (GAs) content, corresponding with accelerated development in transgenic tobacco plants. Moreover, the dwarf phenotype of the transgenic lines that express LmSAPΔA20 and LmSAPΔA20-ΔAN1 under stress conditions was fully restored by the application of exogenous GA3. These findings improve our understanding of the role of LmSAP in regulating GA homeostasis, which is important for regulating plant development under abiotic stress conditions

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

International audiencePyrimidine-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 1H NMR, 13C NMR and ES-HRMS. They were finally tested for their anticoagulant and anti-tyrosinase activities. Significant results have been obtained and the structure-activity relationship (SAR) was discussed with the help of molecular docking analysis. © 201