This review aims to be a comprehensive, authoritative, critical, and readable review of general interest to the medicinal chemistry community because it focuses on the pharmacological, chemical, ...structural and computational aspects of diverse chemical categories as monoamine oxidase inhibitors (MAOIs). Monoamine oxidases (MAOs), namely MAO-A and MAO-B represent an enormously valuable class of neuronal enzymes embodying neurobiological origin and functions, serving as potential therapeutic target in neuronal pharmacotherapy, and hence we have coined the term “Neurozymes” which is being introduced for the first time ever. Nowadays, therapeutic attention on MAOIs engrosses two imperative categories; MAO-A inhibitors, in certain mental disorders such as depression and anxiety, and MAO-B inhibitors, in neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD). The use of MAOIs declined due to some potential side effects, food and drug interactions, and introduction of other classes of drugs. However, curiosity in MAOIs is reviving and the recent developments of new generation of highly selective and reversible MAOIs, have renewed the therapeutic prospective of these compounds. The initial section of the review emphasizes on the detailed classification, structural and binding characteristics, therapeutic potential, current status and future challenges of the privileged pharmacophores. However, the chemical prospective of privileged scaffolds such as; aliphatic and aromatic amines, amides, hydrazines, azoles, diazoles, tetrazoles, indoles, azines, diazines, xanthenes, tricyclics, benzopyrones, and more interestingly natural products, along with their conclusive SARs have been discussed in the later segment of review. The last segment of the article encompasses some patents granted in the field of MAOIs, in a simplistic way.
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•This is a comprehensive review focusing on the pharmacological, chemical, and computational aspects of MAOIs.•We have coined the term “Neurozymes” for the MAOs, which is being introduced for the first time ever in this review.•Chemically diverse category of compounds having MAO inhibitory properties were compiled in this review.•The last section of the review gives an understanding of the patents granted on the MAOs and their inhibitors.
4-Thiazolidinones: The advances continue Tripathi, Avinash C.; Gupta, Shiv Ji; Fatima, Gul Naz ...
European journal of medicinal chemistry,
01/2014, Letnik:
72
Journal Article
Recenzirano
The diversity in the biological response of 4-thiazolidinones has attracted the attention of many researchers to explore this framework for its potential. It is, therefore, of prime importance that ...the study of this topic and the development of new synthetic strategies should be based on the most recent knowledge, emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of the 4-thiazolidinones, predominantly after 2006. The last section of the review encompasses the various patents granted on 4-thiazolidinone analogs/derivatives with World Intellectual Proprietary Organization (WIPO) and United State Patent Trademark Office (USPTO), particularly in the duration of the year 2000 to the year 2012.
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•The manuscript presents a thorough insight into the status of 4-thiazolidinones.•The review has been presented in a manner which is easily understandable.•The review enlightens briefly on some recent patents granted on this nucleus.•The review shall create interest for those planning research on the 4-thiazolidinones.
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.
The present study investigates ameliorative effects of nitric oxide (NO) against zinc oxide nanoparticles (ZnONPs) phytotoxicity in wheat seedlings. ZnONPs exposure hampered growth of wheat ...seedlings, which coincided with reduced photosynthetic efficiency (F
/F
and qP), due to increased accumulation of zinc (Zn) in xylem and phloem saps. However, SNP supplementation partially mitigated the ZnONPs-mediated toxicity through the modulation of photosynthetic activity and Zn accumulation in xylem and phloem saps. Further, the results reveal that ZnONPs treatments enhanced levels of hydrogen peroxide and lipid peroxidation (as malondialdehyde; MDA) due to severely inhibited activities of the following ascorbate-glutatione cycle (AsA-GSH) enzymes: ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase, and its associated metabolites ascorbate and glutathione. In contrast to this, the addition of SNP together with ZnONPs maintained the cellular functioning of the AsA-GSH cycle properly, hence lesser damage was noticed in comparison to ZnONPs treatments alone. The protective effect of SNP against ZnONPs toxicity on fresh weight (growth) can be reversed by 2-(4carboxy-2-phenyl)-4,4,5,5-tetramethyl- imidazoline-1-oxyl-3-oxide, a NO scavenger, and thus suggesting that NO released from SNP ameliorates ZnONPs toxicity. Overall, the results of the present study have shown the role of NO in the reducing of ZnONPs toxicity through the regulation of accumulation of Zn as well as the functioning of the AsA-GSH cycle.
A novel series of N-(N-methylpiperazinoacetyl)-2,6-diarylpiperidin-4-one derivatives (1c–3c and 5c) were synthesized, via base catalyzed nucleophilic substitution of ...N-chloroacetyl-2,6-diarylpiperidin-4-ones (1b–6b) with N-methyl piperazine. The newly synthesized compounds were characterized by FTIR, Mass and NMR spectral studies. All the compounds were screened for their possible analgesic and antipyretic activities. The compound 2c exhibited promising antipyretic activity, comparable to that of paracetamol at 60 mg/kg dose. The compounds 2b and 2c showed significant analgesic profile at a dose of 60 mg/kg and were also found to be more potent than the reference drug, diclofenac sodium. Thus, it can be concluded that the synthesized 2,6-diarylpiperidin-4-ones exhibit promising antipyretic and analgesic activities and could be potential drug candidates.
Various 2,6-diarylpiperidin-4-ones were prepared in a one pot multi-component Mannich reaction by condensing suitably substituted aromatic aldehydes, ketone and ammonium acetate in equimolar ratio, using ethanol as solvent. Display omitted
•One pot synthesis of the title compounds.•Comparable or even better analgesic activity than that of diclofenac sodium.•Antipyretic activity of title compounds similar to that of paracetamol.•Excellent correlation of in vitro hydrolysis profiles with the observed activities.•Excellent correlation of partition coefficient values with the observed activities.
A series of 1,3,5-trisubstituted-2-pyrazoline derivatives
(3a
–
3t
) were synthesized in appreciable yields by substituting N1 position of 2-pyrazoline nucleus with 4-nitrobenzenesulfonylchloride ...using conventional and microwave assisted synthetic approaches. The physicochemical and spectral characterization such as IR, Mass,
1
H-NMR and
13
C-NMR, and elemental analysis, assured the formation of proposed derivatives. Pharmacological studies revealed that compound
3d
exhibited highest antidepressant activity however, compound
3l
was found to be most effective anxiolytic agent at the tested doses (50 and 100 mg/kg b.w.), when compared to the control group. Molecular docking simulations established the possible mechanism of their neuropharmacological effects, with admirable affinity towards MAO-A protein. This was also evidenced from some of the key interactions of these compounds with the amino acid residues Ala68, Tyr69, Phe208, Tyr407 and Tyr444. Moreover, synthesized derivatives showed encouraging pharmacokinetic (ADME) and toxicological (neurotoxicity, carcinogenicity, mutagenicity, reproductive toxicity, irritancy and acute toxicity) parameters as predicted by computational programs. Some of these toxicity studies were further examined in wet laboratory by accomplishing behavioral neurotoxicity studies and acute toxicity studies as per OECD guidelines.
A novel series of 1,3,5-trisubstituted-2-pyrazolines
) 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,
H-NMR,
C-NMR and elemental analysis. During pharmacological evaluation, compound
showed excellent anti-anxiety activity and compound
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
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.
Context: In folk medicine, the stem bark of Streblus asper Lour. (Moraceae) has been reported to possess anticonvulsant activity. However, no systematic/scientific validation is available.
Objective ...This study explores the constituents in the stem bark, their biosassy-guided isolation and their efficacy in neuro-pharmacological disorders, for validating the traditional claims.
Materials and methods: Microwave-assisted extraction (MAE) technique was employed to obtain the crude extract. The n-hexane, dichloromethane and aqueous fractions were prepared and phytoconstituents were ascertained by phytochemical tests. The isolated compound, betulin, was characterized by different physicochemical and spectral methods, including HPTLC. Finally, neuro-pharmacological evaluations were conducted at 100, 200, 400 mg/kg b.w., p.o. (25, 50, 100 mg/kg b.w. for betulin) doses in BALB/c mice.
Results: The n-hexane fraction (400 mg/kg), and isolated compound betulin (100 mg/kg), showed maximum anticonvulsant activity in maximal electroshock (87.84% and 85.14% seizure inhibition), and isoniazid induced convulsion models (88.85% and 83.18% seizure inhibition), respectively. A dose-dependent attenuation of epileptic seizures was observed, probably through GABArgic mechanism of anticonvulsant action. Moreover, the antidepressant study was also conducted using behavioural models and the results expound that n-hexane and dichloromethane fractions (400 mg/kg) significantly reduced the duration of immobility, as compared to the control.
Discussion and conclusion: This study reports some novel aspects like applying an environmentally benign/green approach of MAE, neuro-pharmacological screening and use of docking studies, for the first time, on the plant S. asper. The findings present a rational explanation for its use in traditional medicine, for the management of neuro-pharmacological disorders.
Estrogen receptor–positive mammary gland carcinoma and its involvement in regulation of overexpressed hypoxia-inducible factor-1α and fatty acid synthase level in hypoxia influenced cancer cells are ...the present molecular crosstalk of this entire study. To test the hypothesis, we have proceed our study through chemical activation of prolyl hydroxylase 2 which leads to inhibition of hypoxia-inducible factor-1α and fatty acid synthase in ER+MCF-7 cancer cell line and n-methyl-n-nitrosourea induced mammary gland carcinoma rat model. ER+MCF-7 cells were evident with array of nuclear changes when stained through acridine orange/ethidium bromide. Afterward, JC-1 staining of the cells was evident in mitochondrial depolarization. The cells were arrested in G2/M phase when analyzed with flow cytometry. The morphological analysis of rat mammary gland tissue revealed decrease in alveolar buds, restoration of histopathological features along with intra-arterial cushion. The western blotting and fold change expressions of the genes validating the anticancer efficacy of BBAPH-1 is mediated through mitochondria-mediated apoptosis pathway. BBAPH-1 also modulates the expression of prolyl hydroxylase-2 with significant curtailment of hypoxia-inducible factor-1α, fatty acid synthase expression, and their respective downstream markers. These finding suggest that the BBAP-1-mediated activation of prolyl hydroxylase-2 significantly decreased the level of hypoxia-inducible factor-1α and fatty acid synthase. BBAPH-1 also activates the mitochondria-mediated death apoptosis pathway.
•Thickness dependent sputter yield as well as surface modifications of CaF2thin films due to impact of swift heavy ions has been reported.•Rutherford backscattering spectroscopy (RBS) has been used ...for calculation of sputter yield.•Thermal spike simulations have been done to explain the thickness dependent sputtering.•Crack pattern has been seen by atomic force microscopy (AFM), on surface of irradiated sample which occurs at a particular fluence and increases with increasing fluence.•RBS of irradiated samples reveals that more exposure of substrate is taking place with increasing fluence and thus supports the AFM results.•This formation of cracks has been attributed to swift heavy ions induced plastic or viscous flow driven by capillary forces.
In the present work thin films of CaF2 deposited on Si substrate by electron beam evaporation have been investigated for swift heavy ions induced sputtering and surface modifications. Glancing angle X-ray Diffraction (GAXRD) measurements show that the pristine films are polycrystalline in nature and the grain size increases with increase in film thickness. Rutherford backscattering spectrometry (RBS) of pristine as well as irradiated films was performed to determine the sputter yield of CaF2 and a decrease in sputter yield has been observed with increase in film thickness. Thermal spike model has been applied to explain this. The confinement of energy in the grains having size smaller than the electron mean free path (λ) results in a higher sputtering yield. Atomic force microscopy (AFM) studies of irradiated CaF2 thin films show formation of cracks on film surface at a fluence of 5×1012 ions/cm2. Also RBS results confirm the removal of film from the surface and more exposure of substrate with increasing dose of ions.
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