Mohammad Yusuf

Syntheses and anti-depressant activity of 5-amino-1, 3, 4-thiadiazole-2-thiol imines and thiobenzyl derivatives.

A number of new imine derivatives of 5-amino-1, 3, 4-thiadiazole-2-thiol have been synthesized, and their anti-depressant activity was tested using imipramine as reference drug. Two compounds namely 5-{[1-(4-chlorophenyl)-3-(4-methoxy-phenyl)prop-2-en-1-ylidene]-amino}-5-benzylthio-1, 3,4 -thiadiazole 4i(b) and 5-{[1-(4-chlorophenyl)-3-(4-dimethyl-aminophenyl)-prop-2-en-1-ylidene]amino}-5-benzylthio-1,3,4-thiadiazole 4i(c) have shown significant anti-depressant activity, which decreased immobility time by 77.99% and 76.26% compared to the standard imipramine (82%). All the compounds in the series have passed neurotoxicity tests.

Preparation, characterization, in vivo and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer’s disease model

Background: Alzheimer is a fast growing disease with imprecise chemical treatments. Increased oxidative stress, decrease in acetylcholine concentration, and appearance of amyloidal proteins are reported in pathology of Alzheimer. Chemical drugs are effective but on the cost of detrimental side effects. Purpose: Present research is based on Preparation, characterization, behavioral and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer’s model at a low dose of 2 mg/kg. Methods: Piperine solid lipid nanoparticles were prepared by Emulsification-Solvent Diffusion technique with polysorbate-80 coating to impart Brain specific targeting. Experimental Ibotenic acid induced Alzheimer’s, Force swimming test, superoxide dismutase, acetylcholenesterase enzymatic assays and also Histopathology of brain cortex was conducted to evaluate the Piperine therapeutic effects in Alzheimer’s Disease. Results: Piperine in solid lipid nanoformulation (2 mg/kg equivalent) reduced the SOD values by 504 ± 44.24 m units, p < 0.05, increased the acetylcholenesterase values by 29.24 ± 4.29 µg/mg, p < 0.01 and reduced immobility to 41.36 ± 3.53 s, p < 0.001 and has shown superior results than Donepezil (5 mg/kg). Histopathology studies revealed the reduced plaques and tangles. Conclusions: P-80-PIP-SLN has shown therapeutic effects in Alzheimer via reducing the oxidative stress and reducing the cholinergic degradation at 2 mg/kg dose equivalent.

Plausible antioxidant biomechanics and anticonvulsant pharmacological activity of brain-targeted β-carotene nanoparticles

β-Carotene has been established as a known free radical scavenger with chain-breaking antioxidant properties. It has been documented for the treatment of epileptic convulsions at a 200 mg/kg body weight dose. The reported pathogenesis for epileptic convulsions is oxidative stress. Hence, experimental epileptic convulsions via oxidative stress was induced in albino mice epileptic models (maximal electroshock seizure and pentylenetetrazole [PTZ]). A dose concentration equivalent to 2 mg/kg was efficaciously administered in the form of brain-targeted polysorbate-80-coated poly(d,l-lactide-co-glycolide) nanoparticles. The nanoparticles were prepared by solvent evaporation technique and further characterized for their physical parameters, in-vitro release kinetics, and in-vivo brain release via various standard methods. Normal β-carotene nanoparticles (BCNP) and polysorbate-80-coated β-carotene nanoparticles (P-80-BCNP) of 169.8 ± 4.8 nm and 176.3 ± 3.2 nm in size, respectively, were formulated and characterized. Their zeta potential and polydispersity index were subsequently evaluated after 5 months of storage to confirm stability. In vivo activity results showed that a 2 mg unformulated β-carotene dose was ineffective as an anticonvulsant. However, salutary response was reported from BCNP at the same dose, as the hind limb duration decreased significantly in maximal electroshock seizure to 9.30 ± 0.86 seconds, which further decreased with polysorbate-80 coating to 2.10 ± 1.16 seconds as compared to normal control (15.8 ± 1.49 seconds) and placebo control (16.50 ± 1.43 seconds). In the PTZ model, the duration of general tonic–clonic seizures reduced significantly to 2.90 ± 0.98 seconds by the use of BCNP and was further reduced on P-80-BCNP to 1.20 ± 0.20 seconds as compared to PTZ control and PTZ-placebo control (8.09 ± 0.26 seconds). General tonic–clonic seizures latency was increased significantly to 191.0 ± 9.80 seconds in BCNP and was further increased in P-80-BCNP to 231.0 ± 16.30 seconds, as compared to PTZ (120.10 ± 4.50 seconds) and placebo control (120.30 ± 7.4 seconds). The results of this study demonstrate a plausible novel anticonvulsant activity of β-carotene at a low dose of 2 mg/kg, with brain-targeted nanodelivery, thus increasing its bioavailability and stability.

An Interactive Human Carbonic Anhydrase-II (hCA-II) Receptor – Pharmacophore Molecular Model & Anti-Convulsant Activity of the Designed and Synthesized 5-Amino-1,3,4-Thiadiazole-2-Thiol Conjugated Imine Derivatives

New imines, derived from aromatic aldehyde, chalcones and 5‐amino‐1,3,4‐thiadiazole‐2‐thiol exhibited promising anti‐convulsant activity which is explained through chemo‐biological interactions at receptor site producing the inhibition of human Carbonic Anhydrase‐II enzyme (hCA‐II) through the proposed pharmacophore model at molecular levels as basis for pharmacological activity. The compounds 5‐{1‐(4‐Chlorophenyl)‐3‐[4‐(methoxy‐phenyl)‐prop‐2‐en‐1‐ylidene]amino}‐1,3,4‐thiadiazole‐2‐thiol (2b), 5‐{[1‐(4‐chloro‐phenyl)]‐3‐[4‐(dimethyl‐amino‐phenyl)‐prop‐2‐en‐1‐ylidene]amino}‐1,3,4‐thiadiazole‐2‐thiol (2c) and 5‐{[1‐(4‐chloro‐phenyl)]‐3‐[(4‐amino‐phenyl)‐prop‐2‐en‐1‐ylidene]amino}‐1,3,4‐thiadiazole‐2‐thiol (2f) showed 100% activity in comparison with standard Acetazolamide, a known anti‐convulsant drug. The compounds 2c, 2f also passed the Rotarod and Ethanol Potentiation tests which further confirmed them to be safe in motor coordination activity and safe from generating neurological toxicity.

Polysorbate-80-coated, polymeric curcumin nanoparticles for in vivo anti-depressant activity across BBB and envisaged biomolecular mechanism of action through a proposed pharmacophore model.

Abstract Depression is a modern world epidemic. Its main causative factor is oxidative stress, as reported in study subjects. Natural products are yet to show significant therapeutic effects in comparison with synthetic drugs. Current study deals with the preparation of brain-targeted polysorbate-80-coated curcumin PLGA nanoparticles (PS-80-CUR-NP), and their characterisation via Spectral and optical methods. PS-80-CUR-NP were evaluated against the oxidative stress-mediated depressant (OSMD) activity via Force despair, Tail suspension tests and stress biomarker assay (SOD and catalase activity). A significant reduction in immobility (p < 0.01) in force despair and tail suspension test and a significant increase (p < 0.001 and p < 0.01) in SOD and catalase activity was found and compared with stress control, which confirmed the OSMD activity of PS-80-CUR-NP at 5 mg equivalent dose. Further, AUC(0.5–15 h) curve of brain homogenates estimated the curcumin concentration of 1.73 ng/g C max at T max  3 h via HPLC technique.

Aliphatic and eudesmalolide esters extracted from the roots of Inula racemosa Hook

Background: Phytochemical investigation of hydroalcoholic extract of the root of Inula racemosa Hook. Materials and Methods: Open silica gel column chromatographic techniques with different solvent systems was used for isolation of aliphatic and eudesmalolide esters from hydroalcoholic extract of the root of Inula racemosa. The structure elucidation of the compounds was done on the basis of spectral data analysis, chemical reactions and comparision with literature data. Results: Phytochemical investigation of the hydroalcoholic extract of the root of Inula racemosa Hook. f. led to the isolation of (5z, 13z)-n-decanyl-n-docos-5, 13-dienoate, a new fatty acid ester, two new sesquiterpenic ester identified as 15-[(13z, 18′z, 20′z)-n-tricos-13, 18, 20-trienyl]-eudesmal-4 (11), 6, 12 (13)-trien-8,14-olide-15-oate and 15- [(16′z), (21′z)-n- tetracos-16′, 21′- dienyl]-eudesmal-4 (11) 6, 12 (13)-trien-8, 14-olide-15-oate, two new eudesmanolide ester i.e. 15-[(16z)-n-monadec-16′- enyl]-eudesmal-4 (11) 6, 12 (13)-trien-8,14-olide-15-oate and 15-[(16′z)-n-tetracos-16′- enyl]-endesmal-4 (11), 6, 12 (13)-trien-8,14-olide-15-oate along with the known compound n-Hexadecanyl n-docosanoate. Conclusion: Five new phytoconstituents were identified along with one known compound as aliphatic and eudesmalolide esters from the hydroalcoholic extract of the root of Inula racemosa, as mentioned above.

Isolation and characterization of four novel β-Sitosteryl esters from Salvadora persica Linn.

Abstract Salvadora persica is virtuous to have a variety of phytoconstituents responsible for many biological activities some of them identified particularly while some are still to be acknowledged. A number of steroidal, glycosidic, terpenoids, saponins and functional esters are reported till date. The present study deals with extraction, isolation, and characterisation of four novel steroidal esters by systematic cold extraction of S. persica. The extracted phytoconstituents were characterised by sophisticated spectral UV, IR, NMR and MS, techniques. The reported four new β-Sitosteryl esters SP-2, 3, 5 and 6 were extracted and reported for the first time.

Biomechanistic insights into the roles of oxidative stress in generating complex neurological disorders

Abstract Neurological diseases like Alzheimer’s disease, epilepsy, parkinsonism, depression, Huntington’s disease and amyotrophic lateral sclerosis prevailing globally are considered to be deeply influenced by oxidative stress-based changes in the biochemical settings of the organs. The excess oxygen concentration triggers the production of reactive oxygen species, and even the intrinsic antioxidant enzyme system, i.e. SOD, CAT and GSHPx, fails to manage their levels and keep them under desirable limits. This consequently leads to oxidation of protein, lipids and nucleic acids in the brain resulting in apoptosis, proteopathy, proteasomes and mitochondrion dysfunction, glial cell activation as well as neuroinflammation. The present exploration deals with the evidence-based mechanism of oxidative stress towards development of key neurological diseases along with the involved biomechanistics and biomaterials.

Development and Validation of Rp-HPLC Method for Analysis of Raloxifene in Pharmaceutical Dosage Forms

The aim of present work was to develop and validate a simple, fast and reliable isocratic HPLC method for determination of raloxifene hydrochloride in pharmaceutical dosage form. Chromatographic Separation was achieved by using Agilent technologies model G4288A. Gradient HPLC-1120 , Compact low pressure binary Gradient Pump Consisting Of vacuum in built degasser unit non-PDA UV-vis detector equipped with a manual injection system with 50 uL loop and the eluted analytes for drug was traced by UV detection at 287nm. The method was found to be linear over a wide concentration range (0.1-20 µg/mL) with a correlation coefficient (r) of 0.9995. The LOD and LOQ were 21 and 63 ng/mL for RLX. These results indicate that method is sensitive enough for therapeutic assay. The % RSD values for three selected concentrations were found to be 0.14, 0.51 and 0.75% revealed the high system accuracy. The relative standard deviations (RSD) obtained at three concentrations (n = 6) in the range of 8-10 µg/mL was 0.016-0.018 % for the intraday assay and 0.016-0.024% for interday assay revealed good precision. The specificity was demonstrated that drugs were free of interference from potential impurities. % RSD, theoretical plates and Rmin were not significantly affected when the experimental parameters (such as flow rate, gradient program) were altered and thus concluded that the method was robust.

In silico energy paradigms studies towards stability of nano-encapsulated piperine alkaloid for delivery to Alzheimer?s disease plaque sites in mouse brain

T work describes the pore size measurement by nuclear magnetic resonance (NMR) cryoporometry. Cryoporometry is a superior porosimetry measurement to analyze the pore-size and pore-size distributions (PSDs) with nanoscale pores (1100 nm). NMR cryoporometry, which is non-destructive measurement, is based on the theory of the melting point depression (MPD) of a probe-molecule confined within a pore, which is dependent on the pore diameter. Hydrophilic and/or hydrophobic pore can be measured using a probe-molecule which is sensitive to the hydrophilic and/or hydrophobic circumstance. In order to measure PSDs of mesoporous TiO2 spheres with various pore sizes, NMR cryoporometry measurements were conducted using hydrophobic probe-molecule. MPD was determined by analyzing the variation of the NMR signal intensity with temperature. From the resulting spin-echo intensity versus temperature curves, it was found that maximum MPD of hydrophobic liquid confined within pores of the mesoporous TiO2 decreases with increasing calcination temperature, i.e., the pore size increases with increasing calcination temperature. We also confirmed with Barrett-Joyner-Halenda (BJH) analysis that the pore size of mesoporous TiO2. This trend is in agreement with our NMR cryoporometry results. Overall, these findings indicate that NMR cryoporometry measurement is very effective methods for determining PSDs of mesoporous materials.Z double hydroxides (Zn/Al-LDHs) with 2:1 Zn/Al ratio was prepared by heterocoagulation and modified using different anionic surfactants e.g, sodium dodecyl sulfate (DS) and sodium dodecyl benzene sulfonate (DBS), nitrates in the interlameller space of LDHs was exchanged through excellent anion exchange capacity by DS and DBS. Both hydrophilic and hydrophobized Zn-Al layered double hydroxide were applied as inorganic filler in free emulsion polymerization of aniline monomer. The morphology of the LDHs as well as the prepared nanocomposites was characterized by transmission electron microscope (TEM) and scanning electron microscope (SEM). The X-Ray diffraction (XRD) confirmed the formation of LDHs and totally delaminated into the polymer matrix. The thermal properties were studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Furthermore, the surface area of the prepared nanocomposites were investigated by BET and increased by addition of LDHs compared by neat polyaniline. The electrical conductivity of the prepared nanocomposites was investigated by increasing the ratio of LDHs in the nanocomposite. This work deals with potential applications of these materials, including ion exchange/adsorption, electrochemistry, UV production and conductive coating.Geophagic and cosmetic clays are among potential nanomaterial which occur naturally and are of various forms. The use of these nanoclays is a common practice in both rural and urban areas mostly due to tradition and medicinal reasons. These naturally occurring materials can be valuable sources of nanomaterial by serving as nanocomposites. The need to ascertain the safety of these materials is the motivation for this research. Physical Characterization based on the hue value and microbiological qualities of the nanoclays were carried out. The Microbial analysis of the clay samples showed considerable contamination with both bacteria and fungi with fungal contaminants taking the lead. This observation may not be unlikely due to the ability of fungi species to survive harsher growth conditions than bacteria. ‘Atike pupa’ showed no bacterial growth. The clay with the largest bacterial count was Calabash chalk (Igbanke), while that with the highest fungal count was ‘Eko grey’. The most commonly isolated bacteria in this study were Clostridium spp. and Corynebacterium spp. while fungi included Aspergillus spp. These results are an indication of the need to subject these clay materials to treatments such as heating before consumption or topical usage thereby ascertaining their safety. Keywords—Nanomaterial, clay, microorganism, quality.H three dimensional (3D) lithography is a process to create a 3D structure on a sample substrate by the aid of hologram. The conventional fabrication process such as direct laser beam writing or gray-tone lithography can be used to create one of a kind hologram and multilevel or continuous-level computer generated holograms. Especially, it has been shown that optical gratings can be encoded on the sample surface by two beam interference of a single near infrared femtosecond laser pulse. In general, diffraction gratings were fabricated on optical materials such as silver-halide emulsion, photoresist, and photopolymer. In this work, fabrication of nano-scale holographic gratings on Al2O3 surface using femtosecond laser pulse was demonstrated. Holographic gratings fabrication using two beams interference method on Al2O3 which deposited using ALD device has never been reported. With holographic gratings method, either fabrication time or fabrication cost will be reduced. Moreover, this type of diffraction gratings can be applied for power magnification of the ultra-short laser system.C nanomaterials are defined as those of 1 to 100 nm size. Because of their tiny size and large surface to volume ratio, there is a significant concern that nanomaterials may be responsible for significant human health and environmental risks. It was recently recognized that traditional risk assessment procedures are inadequate for predicting the risks associated with the release of nanomaterials. The root of the problem is in an inadequate application of solid phase chemical principles (e.g., particle size, shape, and functionality) to the risk assessment of nanomaterials. Specifically, the ‘‘solubility’’ paradigm used to evaluate the risks associated with conventional contaminants must be replaced by a ‘‘dispersivity’’ paradigm. Technical challenges for the prediction of environmental risks of engineered nanomaterials include: (a) a lack of accepted measurement techniques and endpoints, (b) limited integration or use of data from published literature for predicting attributes of new materials, and (c) a lack of models to predict attributes. Those deficiencies were addressed in the proposed work by developing wiki style information system. Capability of this system for controlling access and ability for users to access data will be discussed.