N1-benzenesulfonyl-2-pyrazoline hybrids in neurological disorders

A novel series of 1,3,5-trisubstituted-2-pyrazolines (5a-5t) was prepared via Claisen Schmidt condensation, followed by heterocyclization with hydrazine hydrate, substitution of N1 hydrogen of 2-pyrazoline nucleus with 4-chlorobenzenesulfonylchloride, applying conventional and green chemistry approaches. Among the two, microwave assisted organic synthesis (MAOS) emerged as a better synthetic tool in terms of faster reaction rate and high yield. Various physicochemical and spectral studies were conducted to characterize the synthesized derivatives including- IR, Mass, 1H-NMR, 13C-NMR and elemental analysis. During pharmacological evaluation, compound 5b showed excellent anti-anxiety activity and compound 5k exhibited the best antidepressant effect at the tested doses, 50 and 100 mg/kg b.w., being comparable to diazepam and imipramine, respectively. The docking experiments confirmed the probable mechanism of neuropharmacological action, showing excellent affinity towards MAO-A target protein, which was also evidenced from some of the key interactions with binding site residues Ala68, Tyr69 and Phe352. Furthermore, complimentary in silico pharmacokinetic recital without any potential risk of neurotoxicity (as evaluated by rotarod and actophotometer tests), or carcinogenicity, mutagenicity, reproductive toxicity, acute toxicity and irritancy (as predicted by LAZAR and OSIRIS programs) signified their probable use in depression and anxiety disorders

2-Pyrazoline derivatives in neuropharmacology

A novel series of 1,3,5-trisubstituted-2-pyrazoline derivatives (PFC-1 to PFC-16) were synthesized in a three step reaction using conventional and microwave assisted green chemistry approach. The synthesized derivatives were characterized and their chemical structures were established by various physicochemical methods such as IR, Mass, 1H-NMR, 13C-NMR and elemental analysis. The synthesized compounds were tested for their neurophar- macological potential. The compounds exhibited significant antidepressant and anti-anxiety activities against var- ious behavioral in vivo models. Compounds PFC-3 and PFC-12 were found to be the most active derivatives in the series. The 2-pyrazoline analogs, having 2-hydroxyphenyl and anthracen-9-yl substitution at 3rd position while 4-benzyloxyphenyl and 4-methylphenyl substitution at 5th position, were decisive in eliciting good antidepressant and anxiolytic properties, respectively. The docking experiments revealed that the synthesized derivatives were potential inhibitors of MAO-A protein, which plays a central role in managing depression and anxiety disorders. The most potent derivatives were found to be involved in some key interactions with Tyr407, Tyr444, Phe352 and Ala68 amino acid residues at the binding site of MAO-A protein. All the synthesized derivatives successfully passed the pharmacokinetic barriers of absorption, distribution, metabolism and elimination as predicted using in silico techniques without showing any substantial indication of acute and neurotoxicity. This was further confirmed in the laboratory by performing acute toxicity studies as per OECD guidelines

Carbon Nanotropes: A Contemporary Paradigm in Drug Delivery

Discovery of fullerenes and other nanosized carbon allotropes has opened a vast new field of possibilities in nanotechnology and has become one of the most promising research areas. Carbon nanomaterials have drawn interest as carriers of biologically pertinent molecules due to their distinctive physical, chemical and physiological properties. We have assigned the nomenclature “Carbon Nanotropes” to the nanosized carbon allotropes. Carbon nanotropes such as fullerenes, carbon nanotubes (CNTs) and graphenes, have exhibited wide applicability in drug delivery, owing to their small size and biological activity. The nanotherapeutics/diagnostics will allow a deeper understanding of human ills including cancer, neurodegenerative diseases, genetic disorders and various other complications. Recently, nanomaterials with multiple functions, such as drug carrier, MRI, optical imaging, photothermal therapy, etc., have become more and more popular in the domain of cancer and other areas of research. This review is an endeavor to bring together the usefulness of the carbon nanomaterials in the field of drug delivery. The last section of the review encompasses the recent patents granted on carbon nanotropes at United State Patent Trademark Office (USPTO) in the related field

Niosomal Delivery of Isoniazid -Development and Characterization

Purpose: To develop a niosomal formulation for the delivery of isoniazid to achieve effective treatment of tuberculosis. Methods: Niosomes were prepared by reverse phase evaporation method and given a charge with a charge-inducing agent, dicetyl phosphate. Drug entrapment efficiency in the niosomes was determined spectrophotometrically. The niosomes were further characterized for their particle size, polydispersity index (PI) and zeta potential as well as by scanning electron microscopy and stability studies. Furthermore, in vitro drug release and cellular uptake studies on the niosomes by macrophage J744 A were undertaken. Results: Suitable isoniazid niosomes were obtained. The niosomes demonstrated a potential to remain in the treated site for prolonged periods and were also capable of maintaining steady drug concentrations for up to 30 h. Cellular uptake of the drug-loaded niosomes by macrophage cells was as high as 61.8 %, a level that is capable of achieving effective treatment of tuberculosis. Conclusion: The isoniazid niosomes developed are capable of reducing drug dose and toxicity as well as dosing frequency which should bring about improved patient compliance. More importantly, macrophage targeting should be feasible at sites where tuberculosis bacteria are harbored

Niosomal Delivery of Isoniazid - Development and Characterization

Purpose: To develop a niosomal formulation for the delivery of isoniazid to achieve effective treatment of tuberculosis. Methods: Niosomes were prepared by reverse phase evaporation method and given a charge with a charge-inducing agent, dicetyl phosphate. Drug entrapment efficiency in the niosomes was determined spectrophotometrically. The niosomes were further characterized for their particle size, polydispersity index (PI) and zeta potential as well as by scanning electron microscopy and stability studies. Furthermore, in vitro drug release and cellular uptake studies on the niosomes by macrophage J744 A were undertaken. Results: Suitable isoniazid niosomes were obtained. The niosomes demonstrated a potential to remain in the treated site for prolonged periods and were also capable of maintaining steady drug concentrations for up to 30 h. Cellular uptake of the drug-loaded niosomes by macrophage cells was as high as 61.8 %, a level that is capable of achieving effective treatment of tuberculosis. Conclusion: The isoniazid niosomes developed are capable of reducing drug dose and toxicity as well as dosing frequency which should bring about improved patient compliance. More importantly, macrophage targeting should be feasible at sites where tuberculosis bacteria are harbored

Novel 4-Thiazolidinone Derivatives as Anti-Infective Agents: Synthesis, Characterization, and Antimicrobial Evaluation

A series of new 4-thiazolidinone derivatives was synthesized, characterized by spectral techniques, and screened for antimicrobial activity. All the compounds were evaluated against five Gram-positive bacteria, two Gram-negative bacteria, and two fungi, at concentrations of 50, 100, 200, 400, 800, and 1600 µg/mL, respectively. Minimum inhibitory concentrations of all the compounds were also determined and were found to be in the range of 100–400 µg/mL. All the compounds showed moderate-to-good antimicrobial activity. Compounds 4a [2-(4-fluoro-phenyl)-3-(4-methyl-5,6,7,8-tetrahydro-quinazolin-2-yl)-thiazolidin-4-one] and 4e [3-(4,6-dimethyl-pyrimidin-2-yl)-2-(2-methoxy-phenyl)-thiazolidin-4-one] were the most potent compounds of the series, exhibiting marked antimicrobial activity against Pseudomonas fluorescens, Staphylococcus aureus, and the fungal strains. Thus, on the basis of results obtained, it may be concluded that synthesized compounds exhibit a broad spectrum of antimicrobial activity

Isolation, Characterization and Activity of the Flowers of Rhododendron arboreum (Ericaceae)

The flowers of Rhododendron arboreum have been reported to possess certain polyphenolic compounds. Thus, this study was aimed at the anti-microbial and phytochemical screening of the flowers. Important bioactive agents like steroids, saponins and flavonoids were detected in the flowers. Quercetin (a flavonoid) was isolated from the diethyl ether fraction of alcoholic extract by solvent-solvent extraction method. Isolated quercetin was identified and characterized by chemical tests, M.P., TLC, paper chromatography (with authentic marker) and spectroscopic methods like UV-Visible, FT-IR, 1HNMR, 13CNMR and Mass spectroscopy. The anti-microbial activity of the alcoholic and aqueous extract and isolated quercetin were investigated against five bacterial and two fungal strains by agar well-diffusion method. The activity was found to be concentration dependent. Ethanolic extract was found to be more active in comparison to the aqueous extract. Hence, isolation was done with ethanolic extract. The lowest effective concentration of quercetin was found to be 12.5 mg/ml against S. aureus and P. aeruginosa. Both extracts and isolated quercetin were found ineffective against fungal strains. Quercetin may be one of the components responsible for the observed anti-microbial activity of the plant

Syntheses, Characterization and Antimicrobial Evaluation of Some 1, 3, 5-Trisubustituted Pyrazole Derivatives

A series of 1, 3, 5-trisubustituted pyrazole derivatives were synthesized and screened for antimicrobial activity. The compounds (2j-o) were evaluated against two gram-positive and two gram-negative bacteria and one fungus, at concentrations of 10 µg/mL and 50 µg/mL. The compounds were founds to be inactive against P. aeruginosa and A. niger but exhibited moderate activity against B. subtilis, E. coli and S. aureus. It can be concluded that the newly synthesized compounds possess promising antimicrobial activity

Isolation and characterization of quinine from Polygonatum verticillatum: A new marker approach to identify substitution and adulteration

Polygonatum verticillatum (Mahameda) is an important ingredient of Ashtawarga and Ayurvedic formulations. Nowadays, it comes under the category of endangered plants due to large scale and indiscriminate collection of wild material. To overcome the scarcity, substitutes of Mahameda are also commonly used in market. These additives are different from the authentic plant by Ayurvedic and pharmacological theory of drug action, thereby resulting in substitution/adulteration. Substitution is a critical issue in isolation and quantification of the therapeutically active ingredients that can be used as markers in the identification of substitution/adulteration. Methanolic extract of the rhizomes of P. verticillatum was subjected to preliminary phytochemical screening for the detection of phytoconstituents, followed by column chromatography for isolation of the marker. The column was first eluted with pure hexane, and polarity of the solvent was gradually increased. A total of 1180 fractions were collected and pooled on the basis of thin-layer chromatography profile. The single compound was isolated and confirmed by chemical test, melting point, spectral analysis, and comparison with literature. Phytochemical screening of the extract shows the presence of alkaloids, flavonoids, carbohydrates, terpenoids, and phenolics. A pure white crystalline powder was isolated by column chromatography which was characterized as (6-methoxyquinolin-4-yl-8-vinylquinuclidin-2-yl) methanol, i.e. Quinine. The isolated compound, Quinine, was identified as a novel compound in Mahameda as it has not been reported in the genus Polygonatum, till now. It can be used as a marker for the identification of substitution/adulteration and standardization of P. verticillatum

Schizonticidal antimalarial sesquiterpene lactones from <i>Magnolia champaca</i> (L.) Baill. ex Pierre: microwave-assisted extraction, HPTLC fingerprinting and computational studies

<p>The present study explored the schizonticidal potential of traditionally used <i>Magnolia champaca</i> (L.) Baill. ex. Pierre flowers, identifying constituents of interest. The extraction of phytoconstituents was carried out by microwave-assisted technique, isolated via column chromatography, and characterised by various physicochemical, spectral (IR, 1H-NMR and Mass) and chromatographic (HPTLC) techniques. Both the isolated compounds (parthenolide and costunolide diepoxide) exhibited potent schizonticidal antimalarial activity during primary screening in rodent models, with maximum parasitaemia suppression (85.18% and 83.65%, respectively) at a dose of 20 mg/kg body weight when compared to the standard drugs chloroquine and artesunate. <i>In silico</i> techniques were employed to identify the probable biological target and mechanism of action of these isolated compounds. Molecular docking studies also predicted the binding orientations and multi-targeted action of these compounds, in particular costunolide diepoxide with maximum affinity towards SERCA and DHFR proteins. Additionally, favourable <i>in silico</i> ADMET parameters were envisaged through various computational programmes.</p