In vivo Antitumor, Pharmacological and Toxicological Study of Pyrim-ido[4′,5′:4,5]thieno(2,3-b)quinoline with 9-hydroxy-4-(3-diethylaminopropylamino) and 8-methoxy-4-(3-diethylaminopropylamino) Substitutions

2021 ◽  
Vol 21 ◽  
Author(s):  
Hulihalli N. KiranKumar ◽  
Heggodu G. RohitKumar ◽  
Ajay S. Khandagale ◽  
Gopal M. Advirao
Keyword(s):  
Antitumor Activity ◽  
Tumor Regression ◽  
Antioxidant Property ◽  
The Body ◽  
Pharmacological Activities ◽  
In Vivo Models ◽  
Tumor Bearing ◽  
Anti Inflammatory ◽  
Analgesic Activities

Background: We previously synthesized two DNA intercalative pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (PTQ), 9-hydroxy-4-(3-diethylaminopropylamino)pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (Hydroxy-DPTQ) and 8-methoxy-4-(3-diethylaminopropylamino) pyrimido[4’,5’:4,5]thieno(2,3-b) quinolines (Methoxy-DPTQ), and reported their cytotoxicity against cancer cell lines. Objective: In the present study, we sought to analyze the antitumor activity of Hydroxy-DPTQ and Methoxy-DPTQ on Ehrlich’s ascites carcinoma in vivo models, along with other pharmacological activities and toxicity. Methods: Antitumor activity, In vivo antioxidant measurement, Anti-inflammatory activity Analgesic activity, Hematological study, Biochemical parameters, and Nephroprotective ac-tivity. Results: In this study, both the test molecules studied possess potent in vivo antitumor activity without any hematological, biochemical or nephrotoxicity. Significant tumor regression was observed after treatment with both the test molecules, which is suggested by the decrease in the body weight of tumor bearing mice. Mean survival time of mice with tumor was increased from 16 days to 25 and 29 days after 40 and 80 mg/kg Hydroxy-DPTQ treatment, respectively, with a similar result for Methoxy-DPTQ. A dose dependent increase in lifespan upto 80-85% was also displayed by both Hydroxy-DPTQ and Methoxy-DPTQ. Reduction in the tumor volume of mice, upon treatment with molecules also confirmed their antitumor ac-tivity. These molecules also exhibited pharmacological activities such as antioxidant, anti-inflammatory and analgesic activities. Administration of Hydroxy-DPTQ and Methoxy-DPTQ not only reduced the level of lipid peroxidation in tumor bearing mice, but also re-stored the superoxide dismutase, glutathione and catalase levels to normal, substantiating the antioxidant property. Also, treatment of Hydroxy-DPTQ and Methoxy-DPTQ inhibited the pain to approximately 60-80% and 19-33%, respectively. Further, the treatment with Hy-droxy-DPTQ and Methoxy-DPTQ reversed the abnormality in the RBC, WBC and haemo-globin levels, and gentamicin induced nephrotoxicity. Conclusion : Hydroxy-DPTQ and Methoxy-DPTQ are good antitumor molecules with pharmacological properties.

scholarly journals Investigation of the Anti-Inflammatory and Analgesic Activities of Ethanol Extract of Stem Bark of SonapathaOroxylum indicum In Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
K. Lalrinzuali ◽  
M. Vabeiryureilai ◽  
Ganesh Chandra Jagetia
Keyword(s):  
Inflammatory Diseases ◽  
Ethanol Extract ◽  
Stem Bark ◽  
The Body ◽  
Protective Measure ◽  
Analgesic Effects ◽  
Oroxylum Indicum ◽  
Anti Inflammatory ◽  
Analgesic Activities

Inflammation is all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protective measure. However, sustained inflammation leads to several diseases including cancer. Therefore it is necessary to neutralize inflammation. Sonapatha (Oroxylum indicum), a medicinal plant, is traditionally used as a medicine in Ayurveda and other folk systems of medicine. It is commonly used to treat inflammatory diseases including rheumatoid arthritis and asthma. Despite this fact its anti-inflammatory and analgesic effects are not evaluated scientifically. Therefore, the anti-inflammatory and analgesic activities of Sonapatha (Oroxylum indicum) were studied in Swiss albino mice by different methods. The hot plate, acetic acid, and tail immersion tests were used to evaluate the analgesic activity whereas xylene-induced ear edema and formalin induced paw edema tests were used to study the anti-inflammatory activity of Sonapatha. The administration of mice with 250 and 300 mg/kg b.wt. ofO. indicumreduced pain and inflammation indicating that Sonapatha possesses analgesic and anti-inflammatory activities. The maximum analgesic and anti-inflammatory activities were observed in mice receiving 300 mg/kg b.wt. ofO. indicumethanol extract.Our study indicates thatO. indicumpossesses both anti-inflammatory and analgesic activities and it may be useful as an anti-inflammatory agent in the inflammation related disorders.

scholarly journals P006 3D Multicellular intestine-on-a-chip model for disease modelling and drug discovery

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S132-S133
Author(s):  
G Lo Sasso ◽  
L Gijzen ◽  
D Marescotti ◽  
E Naumovska ◽  
E Raineri ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
The Body ◽  
Collagen I ◽  
Epithelial Barrier ◽  
Human Intestine ◽  
In Vivo Models ◽  
Anti Inflammatory

Abstract Background One of the major functions of the human intestine is to provide a protective epithelial barrier between the body and digestive environment. Additionally, the interplay of commensal microbes of the gut microbiome with the gut tissue and host immune system significantly contributes to intestinal homeostasis. Crohn’s disease and ulcerative colitis, collectively referred to as inflammatory bowel diseases, are both associated with increased permeability of the epithelial barrier and dysregulated immune response. Great efforts have been made to develop both in vitro and in vivo models of the human intestine in order to understand the development and underlying pathogenesis of IBD. These efforts have provided valuable insights into multiple aspects of the disease. However, none of these models has been able to capture the complexity and multifactorial nature of IBD. Animal models generally fail to accurately predict the efficacy and toxicity of novel compounds in human tissues, while in vitro human intestinal models developed on porous membranes within Transwell inserts fail to accurately recapitulate and mimic key aspects of the in vivo situation. Methods Here, we present the development and characterisation of a 3D multicellular perfused intestine-on-a-chip model in a microfluidic platform, the OrganoPlate®, and its application for investigating intestinal inflammation. The model described here comprises a coculture of Caco-2 and mucus-secreting HT29-MTX cells in the top compartment of the chip and a coculture of immune-competent cells THP-1 and MUTZ-3 in the bottom compartment, lining a collagen-I ECM in the middle. Results We show that the Caco-2 and HT29-MTX coculture form confluent and polarised tubular structures against the collagen-I ECM in the OrganoPlate®, with a stable barrier function over time as well as the capability to secrete mucus. By exposing the cultures to TNFα and/or IL-1β, we were able to induce an inflammatory state, characterised by cytokine release (IL-8) and a decrease in trans-epithelial electrical resistance. Finally, we proved the applicability of the model in screening anti-inflammatory compounds by its reversibility. Using a well-known anti-inflammatory drug, TPCA-1, we were able to prevent cytokine-induced inflammation. This result was evident from the decreased secretion of IL-8 and retention of barrier function in treated cultures, similar to that observed in untreated cultures. Conclusion Overall, this complex 3D multicellular perfused intestine-on-a-chip model provides the versatile modularity of mimicking key features of intestinal inflammation and can, therefore, further support drug screening efforts and provide a platform for personalised medicine.

A Review on Opuntia Species and its Chemistry, Pharmacognosy, Pharmacology and Bioapplications

2020 ◽  
Vol 16 (8) ◽  
pp. 1227-1244
Author(s):  
Dharmendra Kumar ◽  
Pramod K. Sharma
Keyword(s):  
Human Consumption ◽  
In Vivo Models ◽  
Sugar Amino Acids ◽  
Opuntia Species ◽  
Therapeutic Uses ◽  
Anti Inflammatory ◽  
Online Library ◽  
Different Parts

Background:: Opuntia species, locally known as prickly pear was used for various purposes as food, medicine, beverage, source of dye and animal food. Many studies have revealed its pharmacology activity from time to time. This review is a collection of chemistry, pharmacognosy, pharmacology and bioapplications of the cactus family. Methods: Many sources were used to collect information about Opuntia species such as Pub med, Google scholar, Agris, science direct, Embase, Merk index, Wiley online library, books and other reliable sources. This review contains studies from 1812 to 2019. Results: The plants from the cactus family offer various pharmacological active compounds including phenolic compounds, carotenoids, betalains, vitamins, steroids, sugar, amino acids, minerals and fibers. These bioactive compounds serve various pharmacological activities such as anticancer, antiviral, anti-diabetic, Neuroprotective, anti-inflammatory, antioxidant, Hepatoprotective, antibacterial, antiulcer and alcohol hangover. According to various studies, Opuntia species offer many bioapplications such as fodder for animal, soil erosion, prevention, human consumption and waste water decontamination. Finally, different parts of plants are used in various formulations that offer many biotechnology applications. Conclusion: Different parts of Opuntia plant (fruits, seeds, flowers and cladodes) are used in various health problems which include wound healing, anti-inflammatory and urinary tract infection from ancient times. Nowadays, researches have extended several pharmacological and therapeutic uses of Opuntia species as discussed in this review. Many in-vitro and in-vivo models are also discussed in this review as the proofs of research findings. Various research gaps have been observed in current studies that require attention in the future.

Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo

2019 ◽  
Vol 19 (11) ◽  
pp. 1382-1387
Author(s):  
Ahmet M. Şenışık ◽  
Çiğdem İçhedef ◽  
Ayfer Y. Kılçar ◽  
Eser Uçar ◽  
Kadir Arı ◽  
...  
Keyword(s):  
High Performance ◽  
The Body ◽  
Biological Behavior ◽  
In Vivo Evaluation ◽  
Radiolabeled Peptides ◽  
Tumor Bearing ◽  
Biodistribution Data ◽  
Good Accordance ◽  
Rapid Clearance

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

scholarly journals A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, andIn VivoAntitumor Efficacy and Safety

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Wang ◽  
Ke-Chun Wu ◽  
Bing-Xiang Zhao ◽  
Xin Zhao ◽  
Xin Wang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Therapeutic Efficacy ◽  
Antitumor Efficacy ◽  
Allergic Reactions ◽  
Cremophor El ◽  
Efficacy And Safety ◽  
Tumor Bearing ◽  
Allergic Effect ◽  
Injection Product

The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution,in vivoantitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P<.01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy.

scholarly journals Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1248
Author(s):  
Muhammad Waleed Baig ◽  
Humaira Fatima ◽  
Nosheen Akhtar ◽  
Hidayat Hussain ◽  
Mohammad K. Okla ◽  
...  
Keyword(s):  
In Silico ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Metabolic Reaction ◽  
Datura Innoxia ◽  
In Vivo Models ◽  
Immobility Time ◽  
Anti Inflammatory

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

Evaluation of Anti-inflammatory and Analgesic Activities of Cymbopogon citratus In vivo-Polyphenols Contribution

2015 ◽  
Vol 9 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Gustavo Costa ◽  
Rita Garcia ◽  
Joao Pinto Ferreira ◽  
Telmo Santos ◽  
Fabio Branco ◽  
...  
Keyword(s):  
Cymbopogon Citratus ◽  
Anti Inflammatory ◽  
Analgesic Activities

Polyphenols in Food: Cancer Prevention and Apoptosis Induction

2018 ◽  
Vol 25 (36) ◽  
pp. 4740-4757 ◽  
Author(s):  
Ashita Sharma ◽  
Mandeep Kaur ◽  
Jatinder Kaur Katnoria ◽  
Avinash Kaur Nagpal
Keyword(s):  
Cancer Prevention ◽  
Defense Mechanism ◽  
Antioxidant Property ◽  
The Body ◽  
Water Soluble ◽  
Stress Factors ◽  
In Vivo Studies ◽  
Hydroxyl Groups

Polyphenols are a group of water-soluble organic compounds, mainly of natural origin. The compounds having about 5-7 aromatic rings and more than 12 phenolic hydroxyl groups are classified as polyphenols. These are the antioxidants which protect the body from oxidative damage. In plants, they are the secondary metabolites produced as a defense mechanism against stress factors. Antioxidant property of polyphenols is suggested to provide protection against many diseases associated with reactive oxygen species (ROS), including cancer. Various studies carried out across the world have suggested that polyphenols can inhibit the tumor generation, induce apoptosis in cancer cells and interfere in progression of tumors. This group of wonder compounds is present in surplus in natural plants and food products. Intake of polyphenols through diet can scavenge ROS and thus can help in cancer prevention. The plant derived products can also be used along with conventional chemotherapy to enhance the chemopreventive effects. The present review focuses on various in vitro and in vivo studies carried out to assess the anti-carcinogenic potential of polyphenols present in our food. Also, the pathways involved in cancer chemopreventive effects of various subclasses (flavonoids, lignans, stilbenes and phenolic acids) of polyphenols are discussed.

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