Regioselective One-Pot Synthesis, Biological Activity and Molecular Docking Studies of Novel Conjugates N-(p-Aryltriazolyl)-1,5-benzodiazepin-2-ones as Potent Antibacterial and Antifungal Agents.

Novel 1,2,3-triazolo-linked-1,5-benzodiazepinones were designed and synthesized via a Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction (CuAAC). The chemical structures of these compounds were confirmed by 1H NMR, 13C NMR, HMBC, HRMS, and elemental analysis. The compounds were screened for their in vitro antibacterial and antifungal activities. Several compounds exhibited good to moderate activities compared to those of established standard drugs. Furthermore, the binding interactions of these active analogs were confirmed through molecular docking.

1,5-Benzodiazepines as a platform for the design of carbonic anhydrase inhibitors.

A series of novel N-triazolo-benzene sulfonamides-1,5-benzodiazepines 9a-d and 10d were designed and prepared through the copper-catalyzed azide alkyne cycloaddition click chemistry procedure, reacting the N1 -propargyl-1,5-benzodiazepine 2 and the N1 ,N5 -dipropargyl analog 6 with various benzene sulfonamide azides 8a-d. The synthesized compounds were found to show nanomolar affinity toward relevant isoforms of human carbonic anhydrase such as hCA I, II, IV, VII, IX, and XII. The divalent derivative 10d showed a particularly high inhibitory activity against all hCA isoforms when compared with acetazolamide, and showed potent multivalent effects, better than reported previously for divalent CA inhibitors.

Design, synthesis and biological evaluation of novel 1,2,3-triazole linked coumarinopyrazole conjugates as potent anticholinesterase, anti-5-lipoxygenase, anti-tyrosinase and anti-cancer agents.

A series of new 1,2,3-triazole linked coumarinopyrazole conjugates 4a-e and 5a-e have been synthesized via the Copper(I)-catalysed Alkyne-Azide Cycloaddition (CuAAC). Going through the reaction of compound 2 with the 3-propargyl bromide gave a mixture of propargylated regioisomers 3 + 3' used as a dipolarophile to access to triazoles 4a-e and 5a-e. The structures of the prepared cycloadducts were determined by 1H, 13C and 2D-NMR techniques and by HRMS analysis. All the synthesized derivatives have been evaluated for their anticholinesterase, anti-5-lipoxygenase, anti-tyrosinase, and cytotoxic activities.

1,5-Benzodiazepin-2-ones: Investigation of a Family of Photoluminescent Materials.

Photoluminescent materials, that are now ubiquitous in our everyday life, have particularly attracted the attention of the scientific community these past few years due to potential important applications such as in bioimaging, sensing, or optoelectronics. In this context, relatively few different families of molecules have been reported to exhibit fluorescence in the aggregated or solid-state through the excited-state intramolecular proton transfer (ESIPT) photochemical process. The preparation and subsequent determination of photochemical properties of an underexplored family of 1,5-benzodiazepin-2-one derivatives are reported. From these data and X-ray diffraction analysis study, it emerged that photoluminescence (in the range 520-655 nm) was mostly attributed to ESIPT. The photoluminescent potential of 1,5-benzodiazepin-2-ones, their facile access, and functionalization were demonstrated through the preparation of two fluorogenic probes for the selective detection of biothiols.

Assessment of cochlear effects and extra-auditory disorders in male rats exposed repetitively to low noise.

BACKGROUND: The noise is considered as a factor of environmental stress, causing a wide range of health effects such as acoustic, cardiovascular, nervous and endocrine systems. PURPOSE: The present study was conducted to examine the affects of repeated exposure to noise on the peripheral auditory system, adrenal gland and heart tissue. METHOD: The White strain rats "Wistar" were exposed to chronic and repetitive exposure noise at two different intensity levels of 70 and 85dB (A). The noise level was generated by the Audacity® software to an octave-band noise (8616 kHz). The sound exposure duration was 6 hr/day, 5 days per week for 3 months. Quantitative and qualitative investigations were performed by using electron microscopy. The ganglion neuron counting was examined via light microscopy. RESULTS: The results show that exposure to sound intensities 70 and 85 dB (A) for long periods, lead to changes in the morphological structure of the cochlea (inner ear), adrenal cortex and cardiac tissue which involve cell disruption which over time can lead to pathological effects. CONCLUSION: This study provides morphological evidence that repetitive exposure noise at moderate sound levels to 70 and 85 dB (A) induces changes in the peripheral auditory system, the adrenal cortex and heart tissue.

Aluminum chloride impacts dentate gyrus structure in male adult albino Wistar rats.

To get better insights into the aluminum neurotoxicity, rats were treated with AlCl3 for increasing doses and periods. Body and brain weights, plasma and brain AlCl3 levels were assayed. Light microscopy observation of brain was performed. AlCl3 exposure showed a significant decrease (p < 0.05) on body and brain weight with the highest dose at 18 months. Statistical analysis confirms no significant interaction during 6 months (ρ = 0.357; p > 0.05) while, significant correlation was observed during 12 (ρ = 0.836; p < 0.001) and 18 months (ρ = 0.769; p < 0.001) between body and brain weight. Plasma and brain AlCl3 concentration increased significantly (p < 0.05) with dose and period dependent manner. Statistical analysis confirms significant interaction between brain concentrations of AlCl3 and administrated doses during 6 (ρ = 0.969; p < 0.001), 12 (ρ = 0.971; p < 0.001) and 18 months (ρ = 0.965; p < 0.001). Similar relation was established between plasma AlCl3 concentration and administrated doses during 6 (ρ = 0.970; p < 0.001), 12 (ρ = 0.971; p < 0.001) and 18 months (ρ = 0.964; p < 0.001). Significant relation was confirmed between plasma and brain AlCl3 concentration during 6 (ρ = 0.926; p < 0.001), 12 (ρ = 0.983; p < 0.001) and 18 months (ρ = 0.906; p < 0.001). Morphological alterations mainly targeted the subgranular layer with modulation of the dentate gyrus appearance. This study highlights the toxic effect of AlCl3 on the brain which may affects learning and memory and seems to be different according to dose and duration of exposure.

Development and optimisation of a non conventional extraction process of natural dye from olive solid waste using response surface methodology (RSM).

Dyes obtained from different natural sources have emerged as an important alternative to synthetic dyes. In this study, optimisation of natural colorant non-conventional extraction technique from olive waste was investigated using response surface methodology. The combined effects of extraction conditions on total phenolic content (TPC) and relative color strength (K/S) were studied using a three-level three-factor Box-Behnken design. The optimum conditions for dye extraction were found to be 0.14mol/L, 62.11min, 71.23°C and 4.5g for sodium hydroxide concentration, extraction time, temperature, and mass of the waste, respectively. The efficiency of extraction under these optimum conditions was found to be 1133.86mg/L of phenolics and relative colour strength (K/S) equal to 23.22. Further, Fourier Transform Infrared Spectroscopy was used to identify the major chemical groups in the extracted dye.

[Occupational low back pain in Tunisia]. / La lombalgie post-traumatique professionnelle en Tunisie.

BACKGROUND: In Tunisia, eight researches works, dealing with low back trauma (LBT), have been achieved in some occupational sector activities and only 2 of them have been published. AIM: To synthesize data provided by these 8 works realized between 1998 and 2007, in order to estimate the disorder magnitude and to describe LBT victims profile in Tunisia. METHODS: The global population of study is made of 1357 LBT victims (977 belonging to the private sector and 380 to the public sector). The data collection was carried out according to an uniformed model for the 8 studies. RESULTS: In the public sector, Commission Médicale Centrale data show that LBT account for 4 to 5% of occupational accidents (OA) and that their annual incidence is from 32 to 36/100000. In the private sector, Caisse Nationale d'Assurance Maladie data reveal that LBT account for 7.7% to 9.5% of OA. LBT victim is a male (83%), with an age ranging between 36 and 43.5 years, married (84%), educated up to the secondary educational (91%) with a vertebral disorders history (34%). He belongs to the general-purpose workmen category in 1/2 of cases with an average seniority ranging between 7.8 and 16.2 years. LBT almost subjects, get at least of a sick leave. Work days lost is around 210 days for the private sector and 18 days for the public. The per annum amount versed for each LBT case, within the framework of the Total Temporary incapacity, is of 1449.319 DT and 45% of the subjects profit from a professional reclassification. CONCLUSION: Our results join those of international studies having dealt with LBD in professional environment. In spite of some limiting methodological issues, they allowed us to provide to professionals in occupational health useful data for this occupational risk management.

Neuropharmacological screening of two 1,5-benzodiazepine compounds in mice.

This work investigates whether the two 1,5-benzodiazepine compounds: 4-(2-hydroxyphenyl)-1,5-benzodiazepin-2-one (RG0501) and Benzopyrano [4,3-c] 1,5-benzodiazepine (RG0502) have any neuropharmacological activities. Diazepam and Flunitrazepam were used as drug references. The investigational 1,5-BDZ were tested in vivo for potentiating hexobarbital-induced sleep and pentylenetetrazole (PTZ)-induced seizures. Our study demonstrated that the increase of sleep duration was significantly higher with RG0501 as compared to RG0502. However, RG0502 anticonvulsant effect was more pronounced than that of RG0501 in the range dose of 6.25-37.5 mg.kg(-1). From the 50 mg.kg(-1) dose, RG0502 offered a protection against clonic-tonic seizures as well as lethality (p< or =0.05). The results showed that the required doses to obtain a pharmacological activity were more than those of the references. This difference could be related to the lack of specific substituants responsible for the pharmacological activity in the tested compounds.