25 results on '"Mohammed Samim"'
Search Results
2. Fisetin provides neuroprotection in pentylenetetrazole-induced cognition impairment by upregulating CREB/BDNF
- Author
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Saima Khatoon, Mohammed Samim, Mansi Dahalia, and null Nidhi
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Pharmacology - Published
- 2023
3. Targeted delivery of thermoresponsive polymeric nanoparticle-encapsulated lycopene:in vitroanticancer activity and chemopreventive effect on murine skin inflammation and tumorigenesis
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Sameena Bano, Faheem Ahmed, Mohammed Samim, Farha Khan, and Sandeep C. Chaudhary
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Antioxidant ,Chemistry ,General Chemical Engineering ,medicine.medical_treatment ,04 agricultural and veterinary sciences ,General Chemistry ,Pharmacology ,medicine.disease_cause ,040401 food science ,In vitro ,Lycopene ,Bioavailability ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,0302 clinical medicine ,Apoptosis ,030220 oncology & carcinogenesis ,Lipophilicity ,medicine ,Tumor promotion ,Oxidative stress - Abstract
Naturally occurring lycopene has been reported for its chemopreventive and chemotherapeutic efficiency in various cancers, but its exceptional lipophilicity, poor aqueous solubility, instability, and consequently poor bioavailability limit its usage as a chemopreventive and chemotherapeutic agent. The present study aimed to synthesize co-polymeric nanoparticle-encapsulated formulations of commercial lycopene (NLY) and extracted lycopene (NLX) and evaluate their in vitro anticancer activity and inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin inflammation and tumorigenesis in Swiss albino mice. To prepare the nanoparticle-encapsulated formulations of lycopene, thermosensitive PNIPAAM–PEG-based co-polymeric nanoparticles were synthesized and characterized by FTIR spectroscopy, NMR spectroscopy, DLS, and TEM. Nanolycopene, unlike free lycopene, could be readily dispersed in aqueous media. Nanolycopene demonstrated stronger antioxidant activity and comparable in vitro anticancer efficacy to free lycopene against the melanoma cell line B16. Furthermore, nanolycopene showed comparable reduction of TPA-induced skin edema, expression of COX-2, and oxidative stress response. Additionally, it showed significant inhibition of tumor promotion. It also altered Bax and Bcl2 expressions, which led to the induction of apoptosis. The results also supported that the extracted lycopene-encapsulated nanoparticles may be a good alternative to the expensive commercial lycopene for cancer treatment.
- Published
- 2020
4. Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice
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Ozair Alam, Mohammed Samim, Saima Khatoon, and Nidhi Bharal Agarwal
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0301 basic medicine ,caspase-3 ,fisetin ,Hippocampus ,Pharmacology ,Neuroprotection ,03 medical and health sciences ,chemistry.chemical_compound ,Epilepsy ,0302 clinical medicine ,medicine ,RC346-429 ,PI3K/AKT/mTOR pathway ,Original Research ,Seizure threshold ,pentylenetetrazole ,interleukin ,Kindling ,medicine.disease ,030104 developmental biology ,Neurology ,chemistry ,epilepsy ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,Kindling model ,toll like receptor-4 ,030217 neurology & neurosurgery ,Fisetin - Abstract
Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3′,4′,7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1β, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.
- Published
- 2021
5. Identification and evaluation of glutathione conjugate gamma-<scp>l</scp>-glutamyl-<scp>l</scp>-cysteine for improved drug delivery to the brain
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Mohammed Samim, Afzal Hussain, Tabish Rehman, Taj Mohammad, Md. Imtaiyaz Hassan, Saman Fatima, Deeba Shamim Jairajpuri, Mohammed F. Alajmi, and Farhan Jalees Ahmad
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gamma-L-Glutamyl-L-cysteine ,Antioxidant ,medicine.medical_treatment ,Drug delivery to the brain ,Brain ,General Medicine ,Glutathione ,Human brain ,Tripeptide ,Pharmacology ,Molecular Docking Simulation ,chemistry.chemical_compound ,Drug Delivery Systems ,medicine.anatomical_structure ,Pharmaceutical Preparations ,chemistry ,Structural Biology ,medicine ,Humans ,Cysteine ,Receptor ,Molecular Biology ,Conjugate - Abstract
Glutathione (GU), an endogenous antioxidant tripeptide, is frequently transferred in the human brain through N-methyl-d-aspartate receptor (NMDAR), profusely expressed at the blood–brain barrier (B...
- Published
- 2019
6. Enhancement of the cancer inhibitory effect of the bioactive food component resveratrol by nanoparticle based delivery
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Sandeep C. Chaudhary, Farha Khan, Mohammed Samim, Sameena Bano, and Faheem Ahmed
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Antioxidant ,Carcinogenesis ,medicine.medical_treatment ,Phytochemicals ,Biological Availability ,Apoptosis ,02 engineering and technology ,Resveratrol ,Pharmacology ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Antioxidants ,chemistry.chemical_compound ,Mice ,medicine ,Animals ,Anticarcinogenic Agents ,Skin ,Inflammation ,General Medicine ,021001 nanoscience & nanotechnology ,Bioactive Food Component ,In vitro ,0104 chemical sciences ,Bioavailability ,Oxidative Stress ,chemistry ,Nanoparticles ,Tetradecanoylphorbol Acetate ,0210 nano-technology ,Oxidative stress ,Food Science - Abstract
Naturally occurring bioactive food components such as dietary polyphenols have shown many beneficial biological activities due to their good antioxidant properties. Among them significant attention has been given to resveratrol (RV) in recent years as it plays a promising role in cancer prevention. It has demonstrated anti-proliferative effects, as well as the ability to inhibit the initiation and progression of induced cancer in a wide variety of tumor models. However, the benefits of its therapeutic effects were found to be limited due to its poor pharmacokinetic properties such as poor aqueous solubility, instability and extensive first pass metabolism. To overcome these limitations, the present study aimed to synthesize thermosensitive copolymeric nanoparticle encapsulated formulations of resveratrol-nanoresveratrol (NRV) and evaluate their in vitro anticancer activity and inhibitory effect on 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin inflammation and tumorigenesis in Swiss albino mice. For this purpose PNIPAAM-PEG based thermosensitive copolymeric nanoparticles were synthesized followed by the encapsulation of RV in their hydrophobic core. This enhanced the therapeutic bioavailability of resveratrol. Nanoresveratrol demonstrated stronger antioxidant activity and comparable anticancer efficacy to free resveratrol. Nanoparticles were characterized by IR, NMR, DLS and TEM. The best results were obtained with NRV at significantly lower doses. NRV demonstrated better in vitro anticancer activity against melanoma cell line B16. It showed comparable reduction of TPA induced skin edema, hyperplasia and oxidative stress response. In the promotion phase, a significant reduction was found in tumor incidence and tumor burden in mice pre-treated with NRV. Moreover, at all doses NRV altered Bax and Bcl2 expressions which lead to the induction of apoptosis.
- Published
- 2020
7. Collagen Nanoparticle-Mediated Brain Silymarin Delivery: An Approach for Treating Cerebral Ischemia and Reperfusion-Induced Brain Injury
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Mohd Akhtar, Indu Arora, Shweta Rastogi, Mohammed Samim, Shruti Singh, and Pankaj Rathore
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0301 basic medicine ,food.ingredient ,Ischemia ,ischemia ,Pharmacology ,Neuroprotection ,lcsh:RC321-571 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,food ,medicine ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Research ,Milk Thistle ,Silybum ,General Neuroscience ,apoptosis ,Malondialdehyde ,medicine.disease ,stroke ,Bioavailability ,reperfusion ,030104 developmental biology ,chemistry ,Apoptosis ,Drug delivery ,neuroprotection ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Silymarin is a bioactive constituent isolated from milk thistle (Silybum marinum). Since its discovery, silymarin has been considered a gold standard drug in treating ailments related to the liver, resulting from alcohol consumption and viral hepatitis. This hepatoprotective nature of silymarin arises out of antioxidative and tissue-regenerating properties of silymarin. However, several recent studies have established the neuroprotective link of silymarin, too. Thus, the current investigation was aimed at exploring the neuroprotective effect of nanosilymarin (silymarin encapsulated inside collagen-based polymeric nanoparticulate drug delivery system). The study aimed at bringing out the role of nanoparticles in enhancing the therapeutic effect of silymarin against neuronal injury, originating out of oxidative-stress-related brain damages in focal cerebral ischemia. Collagen-based micellar nanoparticles were prepared and stabilized using 3-ethyl carbodiimide-hydrochloride (EDC-Hcl) and malondialdehyde (MDA) as crosslinkers. Nanoparticles were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy techniques, and the size of nanoparticles was found to be around 48 nm. Male albino Wistar rats were pretreated with three different doses of nanosilymarin of 10, 100, and 1,000 μg/kg b.wt and a dose of free silymarin of 100 mg/kg b.wt intraperitoneally (i.p.) for 7 days. Focal cerebral ischemia was induced using the middle cerebral artery occlusion (MCAO) model on the eighth day for 1 h followed by 24 h reperfusion. The animals were then evaluated for neurobehavioral, infarct analysis, biochemical, histopathological, and immunohistochemical studies. All the above parameters showed remarkable improvement in nanosilymarin-treated groups in comparison to the silymarin-treated group. Nanoparticle encapsulation of drug enhanced neuroprotection by increasing drug bioavailability and targeting. Thus, the present study concluded with satisfactory results, showing the critical role played by nanoparticles in improving the neuroprotection at very low drug doses.
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- 2020
8. Polymeric nanoparticles as a platform for permeability enhancement of class III drug amikacin
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Mohammed Samim, Sushama Talegaonkar, Zeenat Iqbal, Amulya K. Panda, Farhan Jalees Ahmad, and Saman Fatima
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Drug ,Polymers ,Surface Properties ,media_common.quotation_subject ,Microbial Sensitivity Tests ,02 engineering and technology ,Pharmacology ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Escherichia coli ,Tumor Cells, Cultured ,medicine ,Humans ,Particle Size ,Physical and Theoretical Chemistry ,Amikacin ,media_common ,Aminoglycoside ,Surfaces and Interfaces ,General Medicine ,Permeation ,021001 nanoscience & nanotechnology ,Intestinal epithelium ,Anti-Bacterial Agents ,0104 chemical sciences ,Klebsiella pneumoniae ,PLGA ,chemistry ,Permeability (electromagnetism) ,Pseudomonas aeruginosa ,Drug delivery ,Nanoparticles ,0210 nano-technology ,HT29 Cells ,Biotechnology ,medicine.drug - Abstract
Amikacin (A), a water soluble aminoglycoside antibiotic is commercially available for intravenous administration only. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (A-NPs). 1 for oral permeability enhancement of amikacin. The pharmaceutical attributes of the A-NPs revealed particle size, 260.3 ± 2.05 nm, zeta potential, −12.9 ± 1.12 mV and drug content, 40.10 ± 1.87 μg/mg with spherical shape and smooth surface. In vitro antibacterial studies showed that the A-NPs were active against P. aeruginosa, K. pneumoniae and E. coli. The permeation study across rat ileum showed 2.6-fold improvement in Papp for A-NPs than A-S 2 This increase in permeability is due to the uptake of nanoparticles by Peyer’s patches of intestinal epithelium and endocytic uptake via enterocytes. Flow cytometric analysis demonstrated 2.2-fold higher uptake of Rh B-NPs 3 than Rh B-S 4 and elucidated the dominance of enterocytes mediated endocytosis of nanoparticles. Furthermore, stability data collected as per ICH guidelines for three months under accelerated conditions had shown that the A-NPs were stable. The purported drug delivery system hence, seems a promising tool to replace successfully the current intravenous therapy and is used to support relevant patient compliance thereby, adding value to the “patient care at home”.
- Published
- 2018
9. Collagen-curcumin nanocomposites showing an enhanced neuroprotective effect against short term focal cerebral ischemia
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Mohd Akhtar, Shweta Rastogi, Mohammed Samim, Shruti Singh, Indu Arora, and Pankaj Rathore
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0303 health sciences ,business.industry ,General Chemical Engineering ,030302 biochemistry & molecular biology ,Ischemia ,Ischemic injury ,General Chemistry ,Pharmacology ,medicine.disease ,medicine.disease_cause ,Neuroprotection ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,medicine ,Curcumin ,business ,Mode of action ,Reperfusion injury ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
The effectiveness of curcumin in treating cerebral ischemia has been reported in recent studies. However, its mode of action is still not defined. The objective of the present study is to formulate collagen–curcumin nanocomposites which will work effectively against cerebral ischemia/reperfusion injury. Ischemic injury is followed by inflammatory damage and oxidative stress, which together contribute a lot in the pathogenesis of cerebral ischemia and may be considered a good target for treatment. The present study focused on examining the effectiveness of collagen–curcumin nanocomposites stabilized by increasing the degree of crosslinking in reducing oxidative stress associated with brain injury resulting from cerebral ischemia. The collagen nanoparticles were prepared by conjugating collagen on the surface of Tween©80 micelles, and further stabilizing them using crosslinkers. The effectiveness of the prepared nanocomposite was validated by performing infarct analysis followed by biochemical, behavioral, histopathological and immunohistochemical studies. The outcomes of this study are promising for the use of collagen–curcumin nanocomposites in showing neuroprotective potential in treating ischemic injury.
- Published
- 2019
10. Resveratrol loaded nanoparticles attenuate cognitive impairment and inflammatory markers in PTZ-induced kindled mice
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Aarzoo, Shweta Rastogi, Mohammed Samim, Mobin A. Siddiqui, Nidhi Aggarwal, Saliha Manzoor, Dar Junaid Bashir, Juheb Akhter, and Indu Arora
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Male ,Immunology ,Resveratrol ,Pharmacology ,Hippocampus ,Antioxidants ,Mice ,chemistry.chemical_compound ,Epilepsy ,medicine ,Animals ,Humans ,Immunology and Allergy ,Hippocampus (mythology) ,Cognitive Dysfunction ,Cognitive impairment ,Glutathione ,medicine.disease ,Bioavailability ,Disease Models, Animal ,Oxidative Stress ,chemistry ,Pentylenetetrazole ,Collagen ,Nanoparticle Drug Delivery System - Abstract
Resveratrol has been found to exert protective effects in neurological disorders, including epilepsy. However, its poor bioavailability and difficulty in reaching the brain’s targeted location reduce resveratrol’s efficacy substantially. The side effects due to the higher concentration of drugs are another matter of concern. The objective of the present study is to propose solutions to these issues by encapsulating resveratrol in glutathione-coated collagen nanoparticles’ core. The collagen nanoparticles increase the resveratrol’s bioavailability, and glutathione helps in the passage of the encapsulated resveratrol to the target location in the brain. The concentration also substantially reduces due to resveratrol’s encapsulation in glutathione-coated collagen nanoparticles. The encapsulated resveratrol is termed nanoresveratrol. The effectiveness of nanoresveratrol on epilepsy seizures was evaluated through histopathological examinations, ELISA tests, and qRT-PCR tests on the hippocampus of the kindled mice. The novelty of the present study thus lies in (i) the synthesis of nanoresveratrol using glutathione-coated collagen nanoparticles and (ii) the application of synthesized nanoresveratrol in the treatment of epilepsy. The study’s outcome shows that nanoresveratrol has a favorable impact in reducing cognitive impairment in kindled mice, and it is more effective in controlling epilepsy seizures than resveratrol. The p-values of all the nanoresveratrol-given groups of mice (compared with the diseased group) were substantially smaller (∼ 10 - 4 to 10 - 2 ) than the significance level (0.05), indicating that the nanoresveratrol-given groups are significantly different from the diseased group, i.e., the nanoresveratrol has a significant effect on the mice. The concentration of resveratrol also decreases substantially in the proposed nanoformulation. It was observed that even 0.4 mg/kg of nanoformulation of resveratrol is performing better than 40 mg/kg of resveratrol.
- Published
- 2021
11. Embelin ameliorates cognitive dysfunction and progression of kindling in pentylenetetrazol-induced kindling in mice by attenuating brain inflammation
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Seema Jain, Mohammed Samim, Gaurav Kumar Jain, Nidhi Bharal Agarwal, and Ubedul Hoda
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Male ,Hippocampus ,Pharmacology ,Epileptogenesis ,Mice ,03 medical and health sciences ,Behavioral Neuroscience ,0302 clinical medicine ,Dopamine ,Benzoquinones ,Kindling, Neurologic ,medicine ,Animals ,Cognitive Dysfunction ,030212 general & internal medicine ,Pentylenetetrazol ,Seizure threshold ,Kindling ,Chemistry ,Glutamate receptor ,Neurology ,Encephalitis ,Pentylenetetrazole ,Neurology (clinical) ,030217 neurology & neurosurgery ,medicine.drug ,Behavioural despair test - Abstract
Objective This study was conducted to evaluate the effect of embelin (EMB) on various epileptic models and related brain inflammation. Methods Male Swiss albino mice were administered EMB (5, 10, and 20 mg/kg/p.o.) in acute and chronic study for 7 days and 35 days, respectively. Acute study included increasing current electroshock (ICES) and pentylenetetrazol (PTZ)-induced seizure test. Step-down latency (SDL) and forced swim test (FST) were performed to evaluate cognitive functions and depression-like behavior, respectively. Chronic study included PTZ-induced kindling. Levels of inflammatory biomarkers, namely interleukin-1 beta (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were estimated in the hippocampus and cortex of the kindled brains by ELISA technique. Further, neurotransmitters (NTs), namely gamma aminobutyric acid (GABA), glutamate, and dopamine, were estimated by using validated liquid chromatography–mass spectrometry (LC–MS) method followed by ultra-high-performance liquid chromatography (UHPLC). Results Embelin (EMB) treatment increased the seizure threshold to hind limb extension (HLE) in the ICES test and decreased the seizure scores in the kindling experiment. Significantly low levels of IL-1β, IL-1Ra, IL-6, and TNF-α were observed in the hippocampus of PTZ + EMB (10 and 20 mg/kg)-treated groups compared with PTZ+ vehicle-treated group. Significantly lower levels of IL-1Ra, IL-6, and TNF-α compared with PTZ+ vehicle-treated group were observed in the cortex of PTZ + EMB (10 and 20 mg/kg)-treated groups, while IL-1β levels were found to be significantly lower only in the cortex of PTZ + EMB (20 mg/kg)-treated group. Increased levels of dopamine and GABA and decreased levels of glutamate in both hippocampus and cortex were observed in EMB + PTZ-treated groups compared with vehicle + PTZ-treated group. Latency of step down was found to be increased and immobility time in FST was decreased in EMB + PTZ groups compared with vehicle + PTZ group. Conclusion Embelin suppressed epileptogenesis in the kindled mice via neurochemical modulation of neurotransmitters and inhibiting the inflammatory pathway. Further, EMB was also observed to be protecting the kindled animals from cognition and depression-like behavior.
- Published
- 2021
12. Design and synthesis of pyridazinone-substituted benzenesulphonylurea derivatives as anti-hyperglycaemic agents and inhibitors of aldose reductase – an enzyme embroiled in diabetic complications
- Author
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Ameer Ismael, Syed Ovais, Alhamza Dheyaa, G. Bhanuprakash Reddy, Surender Singh, Syed Shafi, Mohammed Samim, Kalicharan Sharma, Ayad Ahmed, Kalim Javed, Pooja Rathore, H. Pushpalatha, Raed Yaseen, and Mymoona Akthar
- Subjects
Male ,0301 basic medicine ,medicine.drug_class ,Pharmacology ,Diabetes Complications ,03 medical and health sciences ,chemistry.chemical_compound ,Aldehyde Reductase ,Lens, Crystalline ,Drug Discovery ,medicine ,Animals ,Hypoglycemic Agents ,Gliclazide ,Rats, Wistar ,IC50 ,Aldose reductase ,Spectrum Analysis ,Area under the curve ,General Medicine ,Sulfonylurea ,Rats ,Pyridazines ,Sulfonylurea Compounds ,030104 developmental biology ,chemistry ,Biochemistry ,Docking (molecular) ,Area Under Curve ,Drug Design ,Female ,Quercetin ,medicine.drug - Abstract
Thirty new aryl-pyridazinone-substituted benzenesulphonylurea derivatives (I-XXX) were synthesized and evaluated for their anti-hyperglycaemic activity in glucose-fed hyperglycaemic normal rats. Twenty-three compounds (III-XI, XIV-XVII, XIX-XXIV, XXVI and XXVIII-XXX) showed more or comparable area under the curve (AUC) reduction percentage (ranging from 21.9% to 35.5%) as compared to the standard drug gliclazide (22.0%). On the basis of docking results, 18 compounds were screened for their in vitro ability to inhibit rat lens aldose reductase. Ten compounds (III-VI, XII, XVI-XVIII, XXI and XXVII) showed ARI activity with IC50 ranging from 34 to 242 μM. Out of these, two compounds IV and V showed best ARI activity which is comparable with that of quercetin. As a result, two compounds (IV and V) possessing significant dual action (anti-hyperglycaemic and aldose reductase inhibition) were identified and may be used as lead compounds for developing new drugs.
- Published
- 2016
13. Synthesis and Biological Evaluation of New Phthalazinone Derivatives as Anti-Inflammatory and Anti-Proliferative Agents
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Alhamzah Dh. Hameed, Mohammed Samim, Mymona Akhtar, Surender Singh, Kalicharan Sharma, Kalim Javed, Raed Yaseen, Pooja Rathore, and Syed Ovais
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0301 basic medicine ,Drug ,medicine.drug_class ,Chemistry ,media_common.quotation_subject ,Pharmaceutical Science ,Nanotechnology ,Carbon-13 NMR ,Pharmacology ,Anti-inflammatory ,In vitro ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,In vivo ,030220 oncology & carcinogenesis ,Drug Discovery ,medicine ,Proton NMR ,Phthalazine ,Etoricoxib ,medicine.drug ,media_common - Abstract
The chemistry of phthalazine derivatives has been of increasing interest since many of these compounds have found many chemotherapeutic applications. So this study aims to synthesize a library of phthalazine derivatives and to investigate their anti-inflammatory and anti-proliferative activities. Sixteen new phthalazinone derivatives (2a-p) were synthesized and tested for their in vitro antiproliferative and in vivo anti-inflammatory activities. All the synthesized compounds were identified and characterized by IR, (1) H NMR, (13) C NMR spectroscopy, and MS. Two compounds, 2b and 2i, showed significant anti-inflammatory activity comparable with that of the standard drug etoricoxib in the carrageenan-induced rat paw edema model at 3 and 5 h, respectively. Three compounds (2h, 2j, and 2g) showed moderate sensitivity toward the renal cancer cell line UO-31.
- Published
- 2016
14. Combinatorial drug delivery strategy employing nano-curcumin and nano-MiADMSA for the treatment of arsenic intoxication in mouse
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Abhishek Yadav, Swaran J.S. Flora, Pramod Kushwaha, and Mohammed Samim
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0301 basic medicine ,Male ,Sodium arsenite ,Curcumin ,chemistry.chemical_element ,Arsenic poisoning ,Pharmacology ,Toxicology ,Arsenic ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Metal poisoning ,Arsenic Poisoning ,medicine ,Animals ,Chelation therapy ,Drug Carriers ,Arsenic toxicity ,Deoxyguanosine ,Drug Synergism ,General Medicine ,medicine.disease ,Glutathione ,Enzymes ,Oxidative Stress ,030104 developmental biology ,chemistry ,Liver ,8-Hydroxy-2'-Deoxyguanosine ,Nanoparticles ,Reactive Oxygen Species ,Succimer ,Combination drug - Abstract
Chelation therapy is the mainstream treatment for heavy metal poisoning. Apart from this, therapy using antioxidant/herbal extracts are the other strategies now commonly being tried for the treatment. We have previously reported individual beneficial efficacy of nanoparticle mediated administration of an antioxidant like 'curcumin' and an arsenic chelator 'monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)' for the treatment of arsenic toxicity compared to bulk drugs. The present paper investigates our hypothesis that a combination drug delivery therapy employing two nanosystems, a chelator and a strong antioxidant, may produce more pronounced therapeutic effects compared to individual effects in the treatment of arsenic toxicity. An in-vivo study was conducted wherein arsenic as sodium arsenite (100 ppm) was administered in drinking water for 5 months to Swiss albino mice. This was followed by a treatment protocol comprising of curcumin encapsulated chitosan nanoparticles (nano-curcumin, 15 mg/kg, orally for 1 month) either alone or in combination with MiADMSA encapsulated polymeric nanoparticles (nano-MiADMSA, 50 mg/kg for last 5 days) to evaluate the therapeutic potential of the combination treatment. Our results demonstrated that co-treatment with nano-curcumin and nano-MiADMSA provided beneficial effects in a synergistic way on the adverse changes in oxidative stress parameters and metal status induced by arsenic.
- Published
- 2018
15. Synthesis and biological evaluation of some new pyrazoline substituted benzenesulfonylurea/thiourea derivatives as anti-hyperglycaemic agents and aldose reductase inhibitors
- Author
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Syed Ovais, Kalim Javed, H. Pushpalatha, Mymoona Akthar, Rafia Bashir, Pooja Rathore, Omprakash Tanwar, G. Bhanuprakash Reddy, Alhamza Dheyaa, Shafiya Yaseen, Mohammed Samim, and Raed Yaseen
- Subjects
Blood Glucose ,Protein Conformation ,Stereochemistry ,Pyrazoline ,Chemistry Techniques, Synthetic ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Aldehyde Reductase ,Drug Discovery ,Animals ,Hypoglycemic Agents ,Enzyme Inhibitors ,Pharmacology ,Aldose reductase ,Chemistry ,Organic Chemistry ,Thiourea ,General Medicine ,Carbon-13 NMR ,Rats ,Anti hyperglycaemic ,Molecular Docking Simulation ,Docking (molecular) ,Proton NMR ,Pyrazoles ,Sorbinil - Abstract
Seventeen new pyrazoline substituted benzenesulfonylurea/thiourea derivatives (2a–q) were synthesized and characterized by elemental analysis and various spectroscopic techniques viz; IR, 1H NMR, 13C NMR, and MS data. Thirteen compounds showed moderate to good anti-hyperglycaemic activity in glucose fed hyperglycaemic normal rats at the dose of 0.05 mM/kg b.w. On the basis of docking results nine compounds (2a, 2c, 2e, 2h, 2k, 2l, 2n, 2o and 2q) were evaluated for their ability to inhibit rat lens aldose reductase. Out of these six compounds (2h, 2k, 2l, 2n, 2o and 2q) were found more effective than the known ARI sorbinil. Five compounds (2h, 2k, 2l, 2n and 2o) showed significant dual action (anti-hyperglycaemic and aldose reductase inhibition).
- Published
- 2014
16. Synthesis and blood glucose lowering activity of some novel benzenesulfonylthiourea derivatives substituted with 4-aryl-1-oxophthalazin-2(1H)yl-ones
- Author
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Mohammed Samim, Rafia Bashir, Kalim Javed, Shafiya Yaseen, Pooja Rathore, and Syed Ovais
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Blood Glucose ,Male ,Stereochemistry ,Rat model ,Medicinal chemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Isothiocyanates ,Drug Discovery ,Acetone ,Animals ,Hypoglycemic Agents ,Rats, Wistar ,Pharmacology ,Glucose lowering ,Aryl ,Benzenesulfonates ,Thiourea ,General Medicine ,Rats ,Glucose ,chemistry ,Elemental analysis ,Drug Design ,Hyperglycemia ,Isothiocyanate ,Anhydrous ,Proton NMR ,Phthalazines ,Female - Abstract
Some new benzenesulfonylthiourea derivatives substituted with phthalazones (2a–q) were synthesized by refluxing the appropriate 4-aryl-1-oxophthalazin-2(1H)yl benzenesulfonamides with isothiocyanate in dry acetone over anhydrous K2CO3. All the synthesized compounds were characterized on the basis of IR, 1H NMR, MS data and elemental analysis. These synthesized compounds (2a–q) at the dose of 20 mg/kg were tested for antihyperglycemic activity in the glucose-fed hyperglycemic normal rat model and among these compounds 2f and 2m showed modest antihyperglycemic activity.
- Published
- 2013
17. Synthesis and anti-inflammatory activity of celecoxib like compounds
- Author
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Syed Ovais, Vinod Nair, Rafia Bashir, Mohammed Samim, Surender Singh, Kalim Javed, Pooja Rathore, and Shafiya Yaseen
- Subjects
medicine.drug_class ,Analgesic ,Antineoplastic Agents ,Pyrazoline ,Pharmacology ,Carrageenan ,Nitric Oxide ,Anti-inflammatory ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Animals ,Edema ,Humans ,Cell Proliferation ,Sulfonamides ,Dose-Response Relationship, Drug ,Molecular Structure ,Tumor Necrosis Factor-alpha ,Melanoma ,Anti-Inflammatory Agents, Non-Steroidal ,General Medicine ,Reference drug ,medicine.disease ,Rats ,chemistry ,Celecoxib ,Cell culture ,Prostaglandins ,Pyrazoles ,Drug Screening Assays, Antitumor ,medicine.drug - Abstract
Nine novel 4-[3-(4-Dimethylamino-phenyl)-5-aryl-4,5-dihydro-pyrazol-1-yl]-benzenesulfonamides (2a-i) were synthesized and evaluated for their anti-inflammatory and antiproliferative activities. These compounds (2a-i) showed moderate to strong anti-inflammatory activity in carrageenan rat paw oedema test. Compounds 2b, 2d and 2g showing comparable anti-inflammatory activity to that of reference drug celecoxib were evaluated for their ulcerogenic and analgesic activities. The effect of 2b, 2d and 2g on the content of NO, TNF-α and PGE2 in exudates from rat paw stimulated by carrageenan was also evaluated. The compound 2c showed considerable antitumor activities against all 60 human tumor cell lines with effective GI50 (MG-MID) value of 3.63 µM. It exhibited maximum activity against melanoma (LOX IMVI and SK-MEL-5) cancer cell lines with GI50 value less than 2 μM.
- Published
- 2012
18. Curcumin encapsulated in chitosan nanoparticles: A novel strategy for the treatment of arsenic toxicity
- Author
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Abhishek Yadav, Swaran J.S. Flora, Vinay Lomash, and Mohammed Samim
- Subjects
Male ,Biogenic Amines ,Curcumin ,Antioxidant ,Sodium arsenite ,medicine.medical_treatment ,Arsenic poisoning ,chemistry.chemical_element ,Pharmacology ,Toxicology ,medicine.disease_cause ,Thiobarbituric Acid Reactive Substances ,Arsenic ,chemistry.chemical_compound ,Arsenic Poisoning ,medicine ,Animals ,Tissue Distribution ,Rats, Wistar ,Arsenic toxicity ,Brain ,General Medicine ,Glutathione ,medicine.disease ,Rats ,Oxidative Stress ,Liver ,chemistry ,Nanoparticles ,Lipid Peroxidation ,Reactive Oxygen Species ,Oxidative stress - Abstract
Water-soluble nanoparticles of curcumin were synthesized, characterized and applied as a stable detoxifying agent for arsenic poisoning. Chitosan nanoparticles of less than 50 nm in diameter containing curcumin were prepared. The particles were characterized by TEM, DLS and FT-IR. The therapeutic efficacy of the encapsulated curcumin nanoparticles (ECNPs) against arsenic-induced toxicity in rats was investigated. Sodium arsenite (2mg/kg) and ECNPs (1.5 or 15 mg/kg) were orally administered to male Wistar rats for 4 weeks to evaluate the therapeutic potential of ECNPs in blood and soft tissues. Arsenic significantly decreased blood δ-aminolevulinic acid dehydratase (δ-ALAD) activity, reduced glutathione (GSH) and increased blood reactive oxygen species (ROS). These changes were accompanied by increases in hepatic total ROS, oxidized glutathione, and thiobarbituric acid-reactive substance levels. By contrast, hepatic GSH, superoxide dismutase and catalase activities significantly decreased on arsenic exposure, indicative of oxidative stress. Brain biogenic amines (dopamine, norepinephrine and 5-hydroxytryptamine) levels also showed significant changes on arsenic exposure. Co-administration of ECNPs provided pronounced beneficial effects on the adverse changes in oxidative stress parameters induced by arsenic. The results indicate that ECNPs have better antioxidant and chelating potential (even at the lower dose of 1.5 mg/kg) compared to free curcumin at 15 mg/kg. The significant neurochemical and immunohistochemical protection afforded by ECNPs indicates their neuroprotective efficacy. The formulation provides a novel therapeutic regime for preventing arsenic toxicity.
- Published
- 2012
19. Synthesis and pharmacological evaluation of some novel 2-pyrazolines bearing benzenesulfonamide as anti-inflammatory and blood glucose lowering agents
- Author
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Syed Ovais, Rafia Bashir, Shafiya Yaseen, Pooja Rathore, Mohammed Samim, and Kalim Javed
- Subjects
Chalcone ,medicine.drug_class ,Hydrochloride ,Organic Chemistry ,Sulfonamide (medicine) ,Pyrazoline ,Pharmacology ,Anti-inflammatory ,chemistry.chemical_compound ,chemistry ,In vivo ,Edema ,medicine ,Moiety ,General Pharmacology, Toxicology and Pharmaceutics ,medicine.symptom ,medicine.drug - Abstract
A series of novel pyrazolines (2a–l) bearing benzenesulfonamide moiety were synthesized by condensing appropriate chalcone (1a–l) with 4-hydrazinobenzenesulfonamide hydrochloride. Structure of all novel synthesized compounds was characterized on basis of elemental analysis data and spectral data (IR, 1HNMR, MS). Compounds (2a–l) were screened for in vivo anti-inflammatory action in carrageenan-induced rat paw edema model and blood glucose lowering action in glucose fed hyperglycemic normal rats. Compounds 2a, 2e, and 2l showed significant anti-inflammatory action (more than 75 %) at 5 h and also showed superior gastrointestinal safety profiles as compared to celecoxib. One compound (2i) was found to exhibit significant blood glucose lowering activity.
- Published
- 2012
20. Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones
- Author
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Mohammad Sarwar Alam, K. K. Pillai, Syed Ovais, Shamim Ahmad, Sameena Bano, I. G. Rathish, Mohammed Samim, Mymoona Akhter, and Kalim Javed
- Subjects
Hydrochloride ,Cell ,Mice, Nude ,Antineoplastic Agents ,Pharmacology ,Mice ,chemistry.chemical_compound ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,medicine ,Animals ,Humans ,Moiety ,Cell Proliferation ,Sulfonamides ,Chemistry ,Melanoma ,Organic Chemistry ,Cancer ,General Medicine ,medicine.disease ,Acute toxicity ,Pyridazines ,Leukemia ,medicine.anatomical_structure ,Cell culture ,Drug Screening Assays, Antitumor - Abstract
Absract A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety ( 2a – h ) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives ( 2a , 2b , 2d , 2g and 2h ) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI 50 value of less than 0.1 μM. It also displayed good activity against leukemia (CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226), non-small cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA-MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI 50 less than 1.0 μM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents.
- Published
- 2012
21. Synthesis and blood glucose lowering activity of some novel benzenesulfonylurea derivatives substituted with 6-aryl-4,5-dihyropyridazin-3(2H)-ones
- Author
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Syed Ovais, Hinna Hamid, Kalim Javed, Mohammad Sarwar Alam, Rafia Bashir, Shafiya Yaseen, and Mohammed Samim
- Subjects
medicine.drug_class ,Aryl ,Organic Chemistry ,Pharmacology ,Carbon-13 NMR ,medicine.disease ,Sulfonylurea ,chemistry.chemical_compound ,chemistry ,Diabetes mellitus ,medicine ,Proton NMR ,Acetone ,Anhydrous ,Gliclazide ,General Pharmacology, Toxicology and Pharmaceutics ,medicine.drug ,Nuclear chemistry - Abstract
Five (2a–e) benzenesulfonylurea derivatives bearing pyridazinone were synthesized by refluxing the appropriate 6-aryl-2-(p-sulfamylphenyl)-4,5-dihydropyridazine-3(2H)-one with benzylisocyanate in dry acetone over anhydrous K2CO3. These compounds were characterized by elemental analysis and various spectroscopic techniques viz; IR, 1H NMR, 13C NMR, and MS data. These compounds (2a–e) at the dose of 20 mg/kg were tested for blood glucose lowering activity in glucose-fed hyperglycemic normal rats. Compound 2b showed more potent anti-hyperglycemic activity than the standard drug gliclazide. The compound 2b was also tested for its hypoglycemic effect in fasted normal rats. It also showed significant hypoglycemic effect (but less than that of gliclazide).
- Published
- 2012
22. Nanoencapsulation of DMSA monoester for better therapeutic efficacy of the chelating agent against arsenic toxicity
- Author
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Vinay Lomash, Abhishek Yadav, A.K. Babbar, Mohammed Samim, Rashi Mathur, Swaran J.S. Flora, Anil K. Mishra, Mahabir Parshad Kaushik, Pramod Kushwaha, and Uma Pathak
- Subjects
Male ,Sodium arsenite ,Materials science ,Stereochemistry ,Biomedical Engineering ,Medicine (miscellaneous) ,chemistry.chemical_element ,Arsenic poisoning ,Bioengineering ,Development ,Pharmacology ,Kidney ,Arsenic ,chemistry.chemical_compound ,Mice ,Metal poisoning ,Arsenic Poisoning ,medicine ,Animals ,General Materials Science ,Chelation ,Chelation therapy ,Rats, Wistar ,Chelating Agents ,Drug Carriers ,Arsenic toxicity ,Kidney metabolism ,Brain ,medicine.disease ,Rats ,chemistry ,Liver ,Nanoparticles ,Rabbits ,Succimer - Abstract
Aims: Exposure to toxic metals remains a widespread occupational and environmental problem in world. Chelation therapy is a mainstream treatment used to treat heavy metal poisoning. This paper describes the synthesis, characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)-encapsulated polymeric nanoparticles as a detoxifying agent for arsenic poisoning. Materials & Methods: Polymeric nanoparticles entrapping the DMSA monoester, which can evade the reticulo-endothelial system and have a long circulation time in the blood, were prepared. Particle characterization was carried out by transmission electron microscopy and dynamic light scattering. An in vivo study was conducted to investigate the therapeutic efficacy of MiADMSA-encapsulated polymeric nanoparticles (nano-MiADMSA; 50 mg/kg orally for 5 days) and comparison drawn with bulk MiADMSA. Swiss albino mice exposed to sodium arsenite for 4 weeks were treated for 5 days to evaluate alterations in blood, brain, kidney and liver oxidative stress variables. The study also evaluated the histopathological changes in tissues and the chelating potential of the nanoformulation. Results: Our results show that nano-MiADMSA have a narrow size distribution in the 50-nm range. We observed an enhanced chelating potential of nano-MiADMSA compared with bulk MiADMSA as evident in the reversal of biochemical changes indicative of oxidative stress and efficient removal of arsenic from the blood and tissues. Histopathological changes and urinary 8-OHdG levels also prove better therapeutic efficacy of the novel formulation for arsenic toxicity. Conclusion: The results from our study show better therapeutic efficacy of nano-MiADMSA in removing arsenic burden from the brain and liver.
- Published
- 2014
23. Solid lipid nanoparticles of anticancer drug andrographolide: formulation, in vitro and in vivo studies
- Author
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Sayeed Ahmad, Rabea Parveen, Mohammed Samim, Farhan Jalees Ahmad, and Zeenat Iqbal
- Subjects
Andrographolide ,Chemistry, Pharmaceutical ,Cmax ,Pharmaceutical Science ,Biological Availability ,Antineoplastic Agents ,Pharmacology ,chemistry.chemical_compound ,Mice ,Pharmacokinetics ,Suspensions ,In vivo ,Cell Line, Tumor ,Drug Discovery ,Solid lipid nanoparticle ,Animals ,Humans ,Particle Size ,Mice, Inbred BALB C ,Chromatography ,Organic Chemistry ,Area under the curve ,Water ,Lipids ,Bioavailability ,body regions ,chemistry ,Solubility ,Area Under Curve ,Lipophilicity ,MCF-7 Cells ,Solvents ,Nanoparticles ,Female ,Diterpenes - Abstract
Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (Cmax), area under the curve (AUC), etc. There was an improvement in Cmax and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The tmax was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.
- Published
- 2013
24. Synthesis and biological evaluation of 4-arylphthalazones bearing benzenesulfonamide as anti-inflammatory and anti-cancer agents
- Author
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Mohammed Samim, Surender Singh, Rafia Bashir, Pooja Rathore, Syed Ovais, Shafiya Yaseen, Vinod Nair, and Kalim Javed
- Subjects
Male ,Stereochemistry ,medicine.drug_class ,Anti-Inflammatory Agents ,Pharmaceutical Science ,Antineoplastic Agents ,Pharmacology ,Anti-inflammatory ,Structure-Activity Relationship ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,medicine ,Animals ,Humans ,Rats, Wistar ,Cell Proliferation ,chemistry.chemical_classification ,Inflammation ,Sulfonamides ,Cyclooxygenase 2 Inhibitors ,Cancer ,Carbon-13 NMR ,medicine.disease ,Rats ,Disease Models, Animal ,Enzyme ,chemistry ,Cell culture ,Celecoxib ,Proton NMR ,Cyclooxygenase 1 ,COX-2 inhibitor ,Phthalazines ,Pyrazoles ,Female ,medicine.drug - Abstract
Nine 4-arylphthalazones bearing benzenesulfonamide (2a–i) were synthesized by the condensation of the appropriate 2-aroylbenzoic acid (1a–i) and 4-hydrazinobenzenesulfonamide in ethanol. The structures of these compounds were elucidated by elemental analysis, IR, 1H NMR, 13C NMR, and MS spectroscopy. Two compounds, 2b and 2i, showed significant anti-inflammatory activity comparable to that of the standard drug celecoxib in the carrageenan-induced rat paw edema model. These compounds (2b and 2i) had selective inhibitory activity towards the COX-2 enzyme. Compound 2b had a better selectivity ratio (COX-1/COX-2) compared to that of celecoxib and can be used as a novel template for the design of selective COX-2 inhibitors. Compounds 2d and 2i were screened for their antiproliferative activity toward 60 human cancer cell lines by the National Cancer Institute (USA). The compounds 2d and 2i displayed mild activity toward the renal cancer cell line UO-31.
- Published
- 2013
25. 6-chloro-7-methyl-3', 4'-dimethoxyflavone - a potent selective COX-2 inhibitor
- Author
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Mohammed Samim, Surender Singh, Rafia Bashir, Vinod Nair, Hinna Hamid, Kalim Javed, Pooja Rathore, Mohammad Sarwar Alam, Shafiya Yaseen, and Syed Ovais
- Subjects
chemistry.chemical_classification ,Male ,Sulfonamides ,Cyclooxygenase 2 Inhibitors ,Pharmacology ,Reference drug ,Flavones ,Rats ,Enzyme ,Chalcones ,chemistry ,Celecoxib ,Edema ,Drug Discovery ,medicine ,COX-2 inhibitor ,Animals ,Pyrazoles ,Female ,medicine.symptom ,Rats, Wistar ,medicine.drug - Abstract
Some unnatural chalcones (1a-q) and flavones (2a-d) have been synthesized and evaluated for their antiinflammatory activity using carrageenan-induced rat paw edema assay. The flavone 2c (6-Chloro-7-methyl-3', 4'- dimethoxyflavone) had higher anti-inflammatory activity and superior gastrointestinal safety profiles than the reference drug celecoxib. Compound 2c showed almost two times better selective inhibitory activity towards COX-2 enzyme than celecoxib. 2'-Hydroxychalcones (1a-h) showed moderate to strong anti-inflammatory activity (38.6-82.4 % at 3h and 52.4–80.2 % at 5h). Among 2'-methoxychalcones (1i-q) 1k and 1q exhibited maximum activity 82.6% (at 3h) and 84.3% (at 5h) respectively.
- Published
- 2012
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