Development of Lipidic Nanoplatform for Intra-Oral Delivery of Chlorhexidine: Characterization, Biocompatibility, and Assessment of Depth of Penetration in Extracted Human Teeth.

Microorganisms are the major cause for the failure of root canal treatment, due to the penetration ability within the root anatomy. However, irrigation regimens have at times failed due to the biofilm mode of bacterial growth. Liposomes are vesicular structures of the phospholipids which might help in better penetration efficiency into dentinal tubules and in increasing the antibacterial efficacy. Methods: In the present work, chlorhexidine liposomes were formulated. Liposomal chlorhexidine was characterized by size, zeta potential, and cryo-electron microscope (Cryo-EM). Twenty-one single-rooted premolars were extracted and irrigated with liposomal chlorhexidine and 2% chlorhexidine solution to evaluate the depth of penetration. In vitro cytotoxicity study was performed for liposomal chlorhexidine on the L929 mouse fibroblast cell line. Results: The average particle size of liposomes ranged from 48 ± 4.52 nm to 223 ± 3.63 nm with a polydispersity index value of <0.4. Cryo-EM microscopic images showed spherical vesicular structures. Depth of penetration of liposomal chlorhexidine was higher in the coronal, middle, and apical thirds of roots compared with plain chlorhexidine in human extracted teeth when observed under the confocal laser scanning microscope. The pure drug exhibited a cytotoxic concentration at which 50% of the cells are dead after a drug exposure (IC50) value of 12.32 ± 3.65 µg/mL and 29.04 ± 2.14 µg/mL (on L929 and 3T3 cells, respectively) and liposomal chlorhexidine exhibited an IC50 value of 37.9 ± 1.05 µg/mL and 85.24 ± 3.22 µg/mL (on L929 and 3T3 cells, respectively). Discussion: Antimicrobial analysis showed a decrease in colony counts of bacteria when treated with liposomal chlorhexidine compared with 2% chlorhexidine solution. Nano-liposomal novel chlorhexidine was less cytotoxic when treated on mouse fibroblast L929 cells and more effective as an antimicrobial agent along with higher penetration ability.

Design, synthesis, and evaluation of novel diphenyl ether derivatives against drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis.

In our efforts to develop druggable diphenyl ethers as potential antitubercular agents, a series of novel diphenyl ether derivatives (5a-f, 6a-f) were designed and synthesized. The representative compounds showed promising in vitro activity against drug-susceptible, isoniazid-resistant, and multidrug-resistant strains of Mycobacterium tuberculosis with MIC values of 1.56 µg/ml (6b), 6.25 µg/ml (6a-d), and 3.125 µg/ml (6b-c), respectively. All the synthesized compounds exhibited satisfactory safety profile (CC50  > 300 µg/ml) against Vero and HepG2 cells. Reverse phase HPLC method was used to probe the physicochemical properties of the synthesized compounds. This series of compounds demonstrated comparatively low logP values. pKa values of representative compounds indicated that they were weak acids. Additionally, in vitro human liver microsomal stability assay confirmed that the synthesized compounds possessed acceptable stability under study conditions. The present study thus establishes compound 6b as the most promising antitubercular agent with acceptable drug-likeness.

Insights on the antioxidant potential of 1, 2, 4-triazoles: synthesis, screening & QSAR studies.

The aligned manuscript reports synthesis, screening and QSAR analysis of twenty six 1, 2, 4-triazole analogues from their respective aromatic carboxylic acids. The structures of synthesized analogues were characterized using physical and spectral analysis. 1, 2, 4-Triazole analogs antioxidant capacity was determined using DPPH radical scavenging assay. Results revealed that out of L, T & VRT series, VRT series of 1, 2, 4-triazoles have significant antioxidant activities when compared with standard ascorbic acid. To obtain structural insights for development of new antioxidants a 2D-QSAR analysis of this dataset of 26 molecules was performed. The 2D-QSAR models correlate with the in vitro results and explain the salient structural features predominant in the molecules responsible for antioxidant activity.

Monastrol mimic Biginelli dihydropyrimidinone derivatives: synthesis, cytotoxicity screening against HepG2 and HeLa cell lines and molecular modeling study.

Biginelli dihydropyrimidinone derivatives as structural analogs of monastrol, a known human kinesin Eg5 inhibitor, were synthesized. IC50 values of the synthesized compounds against the proliferation of human hepatocellular carcinoma and human epithelial carcinoma cell lines were determined through MTT assay. Molecular docking study gave a clear insight into the structural activity relationship of the compounds in comparison with monastrol.

Vasorelaxant and antihypertensive effect of Cocos nucifera Linn. endocarp on isolated rat thoracic aorta and DOCA salt-induced hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Cocos nucifera Linn. (Arecaceae) have long been used in traditional medicine for the treatment of cardio-metabolic disorders. AIM OF THE STUDY: To evaluate the ethanolic extract of Cocos nucifera Linn. endocarp (CNE) for its vasorelaxant activity on isolated rat aortic rings and antihypertensive effects in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats. MATERIALS AND METHODS: Cocos nucifera Linn. endocarp was extracted with ethanol and characterized by HPLC. CNE was examined for its in vitro vascular relaxant effects in isolated norepinephrine, phenylephrine or potassium chloride pre-contracted aortic rings (both intact endothelium and denuded). In vivo anti-hypertensive studies were conducted in DOCA salt-induced uninephrectomized male Wistar rats. RESULTS: Removal of endothelium or pretreatment of aortic rings (intact endothelium) with l-NNA (10µM) or ODQ (10 µM) followed by addition of contractile agonists prior to CNE significantly blocked the CNE-induced relaxation. Indomethacin (10µM) and atropine (1 µM) partially blocked the relaxation, whereas glibenclamide (10 µM) did not alter it. CNE significantly reduced the mean systolic blood pressure in DOCA salt-induced hypertensive rats (from 185.3 ± 4.7 mmHg to 145.6±6.1 mmHg). The activities observed were supported by the polyphenols, viz. chlorogenic acid, vanillic acid and ferulic acid identified in the extract. CONCLUSIONS: These findings reveal that the vasorelaxant and antihypertensive effects of CNE, through nitric oxide production in a concentration and endothelium-dependent manner, is due to direct activation of nitric oxide/guanylate cyclase pathway, stimulation of muscarinic receptors and/or via cyclooxygenase pathway.