Papers by gurusamy mariappan
International Journal of Applied Pharmaceutics
Objective: The current work aimed to prepare and characterize epigallocatechin gallate (EGCG)+ber... more Objective: The current work aimed to prepare and characterize epigallocatechin gallate (EGCG)+berberine-loaded chitosan nanoparticle (EBNP). Methods: The ionic gelation method was adopted. A batch of 17 nanoformulations was prepared by using chitosan as a natural biodegradable polymer and EGCG+berberine as active drug content and characterised. Results: The SEM data proved that the chitosan-based nanoparticles were formed successfully with a spherical shape at 272 nm along with PDI 0.346. The FT-IR spectra confirmed that no drug-polymer interaction was observed. The DSC data proved that the formation of nanoparticles due to the presence of endothermic sharp melting points at 246 °C and 332 °C for EGCG and berberine in the pure form of the drug, whereas the same is absent in nanoformulation. The optimized formulation showed a percentage entrapment efficiency (% EE) for EGCG is 83.91 % and berberine at 90.62%, ZP of the nanoparticle is 11 mV. Conclusion: This study demonstrated that b...
IP International Journal of Comprehensive and Advanced Pharmacology
The world was suffering and People are in great grief due to COVID 19 Pandemic 2020 and 2021 due ... more The world was suffering and People are in great grief due to COVID 19 Pandemic 2020 and 2021 due loss of life, jobs and other related socio-economic issues and now it has been in subsiding mode due to the great weapon COVID vaccine. However omicron is now threatening due to high transmissibility compare to other variants of Corona virus. All of us aware corona Vaccines have been permitted by the regulatory authorities of different countries under emergency situation for restricted use. However by considering Risk-Benefit almost >18 age group most of the people have received the vaccine in few countries but yet to reach out all people in the world. The vaccine has reached the market with exemption category and without detailed exploration of all safety parameters. In the current situation it was learned that most of the corona vaccines are safe and Adverse Events Following Immunization (AEFI) associated with all other vaccines are reported except few serious adverse effects. Coron...
Evaluation of antioxidant potential of pyrazolone derivatives
Journal of advanced pharmaceutical technology & research, 2010
In this article the antioxidant property of pyrazolones derivatives (PYZ1 to PYZ10) are reported.... more In this article the antioxidant property of pyrazolones derivatives (PYZ1 to PYZ10) are reported. It was assessed by estimation of Malonaldehyde (MDA) and 4-Hydroxyl-2-noneal (4-HNE) as lipid peroxidation markers in myocardial ischemic reperfusion injury. The inhibition of lipid peroxidation was compared with the standard ascorbic acid. Among synthesized derivatives PYZ2, PYZ3, PYZ7, PYZ8, PYZ9, and PYZ10 were found to have potent antioxidant effect against MDA marker. In case of 4-HNE, PYZ4, PYZ5, PYZ6, PYZ7, PYZ8, PYZ9 and PYZ10 were found to have effective antioxidant activity and the rest of the compounds are moderately active. Comparatively PYZ7, PYZ8, PYZ9 and PYZ10 are having effective role to control both MDA and 4-HNE generation. All the experimental data were statistically significant at p< 0.05 level. Interestingly, beyond its NSAID property, this study explores the protective role of pyrazolone derivatives in ischemic heart injury.
Saudi Pharmaceutical Journal, 2011
In this paper, we described the pharmacological and toxicological studies of three pyrazolone der... more In this paper, we described the pharmacological and toxicological studies of three pyrazolone derivatives namely PYZ1: 4-[4-N dimethylamino benzylidine]-3-methyl pyrazolin-5(4H)-one, PYZ2: 4-[2-chlorobenzylidine]-3-methylpyrazolin-5(4H)-one and PYZ3: 4-[benzylidine]-3-methylpyrazolin-5(4H)-one derivatives. Analgesic, anti-inflammatory and antipyretic studies of 3-methyl pyrazolone derivatives at 400 mg/kg, p.o. have shown significant activity as compared to control. Amongst three pyrazolone derivatives, PYZ2 was found to be more active. Based on the result of pharmacological studies, PYZ2 was selected for toxicological studies. Acute toxicity studies revealed that methyl pyrazolone derivatives are non-toxic in rats up to 5000 mg/kg, p.o. The subacute toxicity study of PYZ2 showed that decrease in Hb content, RBC and WBC count. In biochemical analysis level of blood glucose and bilirubin reduced where as AST, ALT and alkaline phosphatase level elevated. Histopathological studies revealed that there was mild toxicity on liver and kidney at 1000 mg/kg, p.o.
Indian Journal of Pharmaceutical Sciences, 2008
The plant Kaempferia rotunda Linn. has been explored for its anti oxidant potential in the presen... more The plant Kaempferia rotunda Linn. has been explored for its anti oxidant potential in the present study. The antioxidant property was assessed by lipid peroxidation markers such as malonaldehyde (MDA) and 4-hydroxyl-2-nonenal (4-HNE). The lipid peroxidation byproducts are highly toxic and responsible for various diseases like myocardial infarction, diabetes mellitus, hepatic injury, atherosclerosis, rheumatoid arthritis and cancer. The chemical constituents of the plant were critically and qualitatively analyzed to confi rm the presence of fl avonoids and phenolic derivatives. Hence our objective has been designed to evaluate the antioxidant effect of Kaempferia rotunda linn. and its contribution to control the lipid peroxidation.
ChemInform Abstract: Design, Synthesis and Antidiabetic Evaluation of Oxazolone Derivatives
ChemInform, 2011
Ten novel oxazolone derivatives (III) are synthesized and assayed in vivo for their antidiabetic ... more Ten novel oxazolone derivatives (III) are synthesized and assayed in vivo for their antidiabetic activities.
Computer Applications in Drug Discovery and Development, 2019
Virtual screening plays an important role in the modern drug discovery process. The pharma compan... more Virtual screening plays an important role in the modern drug discovery process. The pharma companies invest huge amounts of money and time in drug discovery and screening. However, at the final stage of clinical trials, several molecules fail, which results in a large financial loss. To overcome this, a virtual screening tool was developed with super predictive power. The virtual screening tool is not only restricted tool small molecules but also to macromolecules such as protein, enzyme, receptors, etc. This gives an insight into structure-based and Ligand-based drug design. VS gives reliable information to direct the process of drug discovery (e.g., when the 3D image of the receptor is known, structure-based drug design is recommended). The pharmacophore-based model is advisable when the information about the receptor or any macromolecule is unknown. In this ADME, parameters such as Log P, bioavailability, and QSAR can be used as filters. This chapter shows both models with various representative examples that facilitate the scientist to use computational screening tools in modern drug discovery processes.
Abstract 3325: Combination of DNMT and HDAC inhibitors reprogram cancer stem cell signaling to overcome drug resistance
Cancer Research, 2016
In recent years, impressive technical advancements have been made in the isolation and validation... more In recent years, impressive technical advancements have been made in the isolation and validation of the mammary stem cells (MaSCs) and cancer stem cells (CSCs). However, the signaling pathways that regulate stem cell self-renewal are largely unknown. Further, CSCs are believed to contribute to resistance to chemotherapy and radiation therapy. However, an effective therapeutic strategy to overcome this resistance is yet to be identified. We have recently discovered that the DNA methyltransferases, especially DNMT1, play critical role in MaSCs and CSCs self-renewal and targeted deletion of this gene impaired mammary tumor formation by inhibiting CSCs formation. However, the molecular mechanism(s) by which DNMTs control CSCs and the therapeutic relevance of DNMTs inhibitors in regulation of CSCs and overcome drug resistance are also largely unknown. In this study, using MMTV-Neu-Tg mouse mammary tumor model, we found that both luminal progenitor and basal stem cells are susceptible to genetic and epigenetic modifications, which leads to activation of un-activated Neu-Tg into transformed tumor forming phenotype. Combination of 5-Azacytidine, a DNMT inhibitor, and butyrate, a HDAC inhibitor, markedly reduces CSCs and consequently increases the overall survival of the animal. RNA-seq analysis of the CSCs treated with 5-AzaC+butyrate provides evidence that combined inhibition of DNMTs and HDACs reduces CSCs pool in the mammary gland by blocking growth-promoting signaling molecules like RAD51AP1 and SPC25. RAD51AP1 and SPC25, which are known to play a key role in DNA damage repair and kinetochore assembly, are significantly overexpressed in breast tumor tissues and associated with decreased overall patients’ survival. Further, these two genes are overexpressed in Tamoxifen and Taxol resistant human breast cancer cell lines. Functional inactivation of these genes in breast caner cells facilitates chemotherapy-induced apoptosis and reduces tumor growth. Overall, our studies provide strong evidence that breast CSCs (both basal stem cells and luminal progenitor cells) are susceptible for genetic and epigenetic modifications and associated with resistance to chemo- and radiotherapy. Thus, combination of DNMT and HDAC inhibitors can serve as an effective therapeutic strategy to block mammary tumor growth and to overcome drug resistance by inhibiting CSCs. Citation Format: Rajneesh Pathania, Ravindra B. Kolhe, Sabarish Ramachandran, Gurusamy Mariappan, Priyanka Thakur, Puttur D. Prasad, Vadivel Ganapathy, Muthusamy Thangaraju. Combination of DNMT and HDAC inhibitors reprogram cancer stem cell signaling to overcome drug resistance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3325.
Cancer research, Jun 1, 2016
Recently, impressive technical advancements have been made in the isolation and validation of mam... more Recently, impressive technical advancements have been made in the isolation and validation of mammary stem cells and cancer stem cells (CSC), but the signaling pathways that regulate stem cell self-renewal are largely unknown. Furthermore, CSCs are believed to contribute to chemo- and radioresistance. In this study, we used the MMTV-Neu-Tg mouse mammary tumor model to identify potential new strategies for eliminating CSCs. We found that both luminal progenitor and basal stem cells are susceptible to genetic and epigenetic modifications, which facilitate oncogenic transformation and tumorigenic potential. A combination of the DNMT inhibitor 5-azacytidine and the HDAC inhibitor butyrate markedly reduced CSC abundance and increased the overall survival in this mouse model. RNA-seq analysis of CSCs treated with 5-azacytidine plus butyrate provided evidence that inhibition of chromatin modifiers blocks growth-promoting signaling molecules such as RAD51AP1 and SPC25, which play key roles ...
The present study investigates the cardioprotective effect of pyrazolone derivatives (PYZ1-PYZ10)... more The present study investigates the cardioprotective effect of pyrazolone derivatives (PYZ1-PYZ10) on plasma lipid profile, serum marker enzymes, endogenous enzymatic and non-enzymatic antioxidants in cardiac tissues against isoproterenol (ISO) induced myocardial ischemic injury in rats. Pretreatment with the pyrazolone derivatives at 10 mg/kg body weight for 5 days prevented the elevation of serum marker enzymes namely lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) in myocardial injured rats. ISOinduced animals exhibited decreased levels of superoxide dismutase (SOD) and glutathione (GSH) in the heart, which were restored to near normal levels following treatment with pyrazolone derivatives. These derivatives also attenuated lipid peroxidation (LPO) in the heart and improved the imbalance in lipid profile (TG, LDL, VLDL, HDL) caused by ISO. These findings revealed the cardioprotective effect of pyrazolone derivatives against isoproterenol induced myocardial injury.
A novel series of benzothiazole derivatives were synthesized and assayed in vivo to investigate t... more A novel series of benzothiazole derivatives were synthesized and assayed in vivo to investigate their hypoglycemic activity by streptozotocin-induced diebetic model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well known antidiabetic agent as a reference drug. All the compounds were effective, amongst them 3d showed more prominent activity at 100 mg/kg p.o. The experimental results are statistically significant at p<0.01 and p<0.05 level.
Indian Journal of …, 2011
Abstract:[1-(N-substituted amino) methyl]-2-ethyl benzimidazole derivatives 1-10 have been synthe... more Abstract:[1-(N-substituted amino) methyl]-2-ethyl benzimidazole derivatives 1-10 have been synthesized by the condensation of 2-ethyl benzimidazole with substituted primary and secondary amines. Their structures have been elucidated by UV-Vis, IR, 1 H NMR and ...
Indian Journal of Pharmaceutical Sciences, 2006
Combinatorial chemistry is a novel synthetic strategy which leads to produce a large number of ch... more Combinatorial chemistry is a novel synthetic strategy which leads to produce a large number of chemical libraries with predetermined structures. The advances in the research of combinatorial library synthesis and screening methods have enabled the medicinal chemists to identify highly active compounds rapidly. This method has revolutionized basic research and drug discovery. A number of combinatorial methods have been developed to boost the morale of medicinal chemists. Out of those, positional scanning synthesis plays a significant role to generate libraries from libraries. This approach is capable of producing infinite libraries. Our aim is to explore this method to understand the principle of synthesis and deconvolution screening methods to identify individual active compounds.
ChemInform
All the synthesized compounds (III), especially derivatives (IIIb), show effective neuropharmacol... more All the synthesized compounds (III), especially derivatives (IIIb), show effective neuropharmacological activities.
Journal of advanced pharmaceutical technology & research, 2010
The formazan derivatives (FM1-FM5) were synthesized by the reaction of benzaldehyde phenylhydrazo... more The formazan derivatives (FM1-FM5) were synthesized by the reaction of benzaldehyde phenylhydrazone with substituted aromatic and hetero aromatic amines. The structures of the synthesized compounds were then elucidated using UV, IR, (1)H NMR and mass spectral data. The synthesized derivatives were screened for anticonvulsant, antibacterial and antiviral activities. All the compounds showed remarkable antibacterial activity at 250 μg/ml, but FM4 and FM3 did not show any inhibition on Staphylococcus aureus and Vibriocholera, respectively. All the compounds showed significant anticonvulsant effect at 100 mg/kg p.o. and the experimental data were statistically significant at P<0.001 level. But none of the compounds was effective against Japanese encephalitis virus.
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Papers by gurusamy mariappan