Synthesis of quinazolinones derivatives an antiproliferative agent against human lung carcinoma cells

2,3‐Dihydroquinazolin‐4(1H)‐one derivatives (3a-p) were synthesized in excellent yields. These compounds were screened for antiproliferative activity against A549 cells and were found as potent cytotoxicity. Compounds A4, A8, A10 found to be more promising antiproliferative against the lung carcinoma A549 cells. IC50 values for compounds A4, A8 and A10 were found to be 8.6, 8.9 and 8.1 μg/L against A549 cells, respectively

Implementation Of Anonymous Vehicle Reporting And Communication System For Wrongly Parked Vehicle

Improper parking can cause several issues and problems, including Reduced Accessibility, Inconvenience for Other Drivers, Public Transportation Disruption, Environmental and Aesthetic Concerns, Public Perception, and Traffic Congestion. Addressing these issues typically calls for a combination of traffic management, public awareness campaigns, law enforcement, smart urban design, and community involvement to preserve the successful and safe usage of public spaces

Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling

FGF signaling in neurons is regulated by Survival Motor Neuron, a component of a complex that regulates snRNP biogenesis and FGF receptor expression

Rescue of Photoreceptor Degeneration by Curcumin in Transgenic Rats with P23H Rhodopsin Mutation

The P23H mutation in the rhodopsin gene causes rhodopsin misfolding, altered trafficking and formation of insoluble aggregates leading to photoreceptor degeneration and autosomal dominant retinitis pigmentosa (RP). There are no effective therapies to treat this condition. Compounds that enhance dissociation of protein aggregates may be of value in developing new treatments for such diseases. Anti-protein aggregating activity of curcumin has been reported earlier. In this study we present that treatment of COS-7 cells expressing mutant rhodopsin with curcumin results in dissociation of mutant protein aggregates and decreases endoplasmic reticulum stress. Furthermore we demonstrate that administration of curcumin to P23H-rhodopsin transgenic rats improves retinal morphology, physiology, gene expression and localization of rhodopsin. Our findings indicate that supplementation of curcumin improves retinal structure and function in P23H-rhodopsin transgenic rats. This data also suggest that curcumin may serve as a potential therapeutic agent in treating RP due to the P23H rhodopsin mutation and perhaps other degenerative diseases caused by protein trafficking defects

Influence of Lipophilicity on Drug Partitioning into Sclera, Choroid-Retinal Pigment Epithelium, Retina, Trabecular Meshwork, and Optic Nerve

In vitro bovine eye tissue/phosphate-buffered saline, pH 7.4, partition coefficients (Kt:b), in vitro binding to natural melanin, and in vivo delivery at 1 h after posterior subconjunctival injection in Brown Norway rats were determined for eight β-blockers. The Kt:b was in the order intact tissue, dry weight method ≥ intact tissue, wet weight method corrected for tissue water and drug in tissue water ≫ intact tissue, wet weight method > homogenized tissue. In intact tissue methods, Kt:b followed the order choroid-retinal pigment epithelium (RPE) > trabecular meshwork > retina > sclera ∼ optic nerve; propranolol > betaxolol > pindolol ∼ timolol ∼ metoprolol > sotalol ∼ atenolol ∼ nadolol. Intact tissue, wet weight log (Kt:b) correlated positively with log D for all tissues (R2 of 0.7–0.9). Log (melanin binding capacity) correlated positively with choroid-RPE log (Kt:b) (R2 of 0.5). With an increase in concentration, Kt:b decreased in trabecular meshwork for all β-blockers and for some lipophilic β-blockers in choroid-RPE and sclera. With an increase in drug lipophilicity, in vivo tissue distribution increased in choroid-RPE, iris-ciliary body, sclera, and cornea but exhibited a declining trend in retina, vitreous, and lens. In vitro bovine intact tissue, wet weight Kt:b correlated positively with rat in vivo tissue/vitreous humor distribution for sclera, choroid-RPE, and retina (R2 of 0.985–0.993). In vitro tissue partition coefficients might be useful in predicting in vivo drug distribution after trans-scleral delivery. Less lipophilic solutes exhibiting limited nonproductive binding in choroid-RPE might exhibit greater trans-scleral delivery to the retina and vitreous

Sodium fluorescein concentrations in choroid-retina, vitreous, and anterior chamber regions after intravitreal injection.

<p>At 2 minutes of injection, the vitreous region had the highest concentration (1512±1517 ng/ml). Choroid-retina and anterior chamber regions had peak concentrations of 103±45 ng/ml and 24±8 ng/ml, respectively, at 27.5 minutes and 10 minutes. The baseline values for choroid, vitreous, and anterior chamber were 6.5 (±5.53), 1.65 (±0.78), 0.5 (±0.31) ng/ml, respectively. Data is represented as mean ± S.D. for n = 4. Inset shows NaF levels in choroid-retina and anterior chamber.</p

Influence of Drug Solubility and Lipophilicity on Transscleral Retinal Delivery of Six Corticosteroids

The influence of drug properties including solubility, lipophilicity, tissue partition coefficients, and in vitro transscleral permeability on ex vivo and in vivo transscleral delivery from corticosteroid suspensions was determined. Solubility, tissue/buffer partition coefficients for bovine sclera and choroid-retinal pigment epithelium (CRPE), and in vitro bovine sclera and sclera-choroid-retinal pigment epithelium (SCRPE) transscleral transport were determined at pH 7.4 for triamcinolone, prednisolone, dexamethasone, fluocinolone acetonide, triamcinolone acetonide, and budesonide in solution. Ex vivo and in vivo transscleral delivery was assessed in Brown Norway rats after posterior subconjunctival injection of a 1 mg/ml suspension of each corticosteroid. Corticosteroid solubility and partition coefficients ranged from ∼17 to 300 μg/ml and 3.0 to 11.4 for sclera and from 7.1 to 35.8 for CRPE, respectively, with the more lipophilic molecules partitioning more into both tissues. Transport across sclera and SCRPE was in the range of 3.9 to 10.7% and 0.3 to 1.8%, respectively, with the transport declining with an increase in lipophilicity. Ex vivo and in vivo transscleral delivery indicated tissue distribution in the order CRPE ≥ sclera > retina > vitreous. Tissue partitioning showed a positive correlation with drug lipophilicity (R2 = 0.66–0.96). Ex vivo and in vivo sclera, CRPE, retina, and vitreous tissue levels of all corticosteroids showed strong positive correlation with drug solubility (R2 = 0.91–1.0) but not lipophilicity (R2 = 0.24–0.41) or tissue partitioning (R2 = 0.24–0.46) when delivered as suspensions. In vivo delivery was lower in all eye tissues assessed than ex vivo delivery, with the in vivo/ex vivo ratios being the lowest in the vitreous (0.085–0.212). Upon exposure to corticosteroid suspensions ex vivo or in vivo, transscleral intraocular tissue distribution was primarily driven by the drug solubility

Representative fluorophotometry scans attained using Fluorotron Master™ in Sprague Dawley rat eye.

<p>Scans are for (A) blank eye showing autofluorescence, (B) eyes immediately after injection of NaF in suprachoroidal, posterior subconjunctival, or vitreous region, (C) eyes 30 minutes after injection of NaF in suprachoroidal, posterior subconjunctival, or vitreous region. Data in panel A is an average for n = 6, and in B and C it is an average for n = 4. Representative time dependent scans after injection of NaF in (D) suprachoroidal, (E) posterior subconjunctival, and (F) vitreous regions are also shown. Blank eye scan shows the autofluorescence of choroid-retina, lens, and cornea regions.</p