Journal of Applied Pharmaceutical Science

Published by Open Science Publishers LLP

Online ISSN: 2231-3354


Clinical effectiveness and safety of brimonidine (0.2%) versus Dorzolamide (2.0%) in primary open angle
  • Article

October 2011


144 Reads

N. Sharma


A. Gupta


G. Singh
A Comparison of efficacy & tolerability of brimonidine (0.2%) versus dorzolamide (2.0%) in primary open angle glaucoma or ocular hypertension. In this open, randomized, cross over comparative study, 30 subjects of primary open angle glaucoma with IOP > 22 mmHg were taken. The patients fulfilling the inclusion criteria and after verifying the exclusion criteria were included in the study after a written informed consent. These subjects were randomized to receive brimonidine (0.2%) TDS or dorzolamide (2.0%) TDS for 4 weeks. After a wash out period of 4 weeks the subjects were crossed over to other therapy .The IOP was measured at 8.00 am before dosing and at 10.00 am i.e. 2 hours after dosing at each baseline and at the end of each treatment period. Monotherapy with brimonidine (0.2%) TDS and dorzolamide (2.0%) TDS given for 4 weeks had caused overall reduction in IOP of 5.833+2.102mmHg (23.48%) and 5.433+ 2.582mmHg (22.42%) respectively at peak levels. The difference is statistically insignificant (p>0.05). Overall monotherapy with brimonidine and dorzolamide appear to produce equivalent IOP lowering efficacy and have well tolerated adverse effect profile, although a trend was observed at 10.00 a.m. of greater brimonidine efficacy compared with dorzolamide.

Possible involvement of leptin in a Mas-receptor agonist, AVE-0991-induced improvement in dyslipidemia and cardiomyopathy in STZinduced diabetic rats

November 2013


57 Reads

Present study was designed to investigate the possible involvement of leptin in the pharmacological activation of Mas-receptor in STZ-diabetic rats, with cardiomyopathy. A single administration of STZ (50 mg/kg, i.p.) produced diabetes which leads to cardiomyopathy after 8 weeks. Estimation of serum glucose has been used as a marker of hyperglycemia. Cardiomyopathy was assessed by measuring LV collagen content, absolute LV weight, LVW/BW ratio, LVDP, dp/dtmax and dp/dtmin. Furthermore, serum triglyceride, serum cholesterol and serum HDL levels were estimated as an index of dyslipidemia. Rat serum leptin was quantitatively estimated by using enzyme-linked immunosorbent assay (ELISA) kit. STZ-diabetic rats were associated with significant hyperglycemia, hypertriglyceridemia, decreased cardiac functions and decreased serum leptin level. Both the low and high dose AVE-0991 treatment, significantly decreased hyperglycemia and increased serum leptin level in diabetic rats. Whereas, AVE-0991 only at high dose significantly improved lipid profile and cardiac function. on the basis of above, it may be concluded that downstream activation of leptin may be responsible for the beneficial effect of AVE-0991, a Mas-receptor agonist in STZ-induced diabetic cardiomyopathy in rats.

Fig. 1: Synthesis of 4-bromo-5-ethyl-2-(ethylamino)-5-methyl-5H-1,2-oxaphosphole 2-oxide (2) (Br-oxph-1). Pail-red cryst., m.p. ( o C) uncorrected 120-122; Anal. Calcd. for C 10 H 19 BrNO 2 P; (Mr = 268.07): P 11.55, N 5.22, Hal. 29.80 Found: P 11.38, N 5.12, Hal. 29.43%; 1.21 g (82%), IR(KBr): ν max /cm-1 1590, 1260, 1000; 1 H NMR(CDCl 3 ): δ/ppm 5.35 (dd, 2 J HP 27.7Hz, 3 J HH 3.75Hz, 1 H), 3.79 (m, 1 H); 2.93 (m, 3 J HP 13.6Hz, 2H), 1.00 (tr, 3 J HH 7.0Hz, 3H); 1.70 (m, 2H), 0.69 (tr, 3 J HH 6,5Hz, 3H); 1.23 (s, 3H); 31 P NMR(CDCl 3 ) δ/ppm: 31 P 30.09. 
Table 1 : Effect of treatment with Br-oxph-1 (8.23 × 10 3 μM, for 24 h) on mitotic index in root tip meristematic cells of Allium cepa L. 
Fig. 2: Inhibition of root growth of Triticum aestivum induced by treatment with different concentrations of Br-oxph-1 for 96 h; *Р ≤ 0.05. 
Table 2 : Effects of treatment with Br-oxph-1 (8.23 × 10 3 μM, for 24 h) on phase indices in root tip meristematic cells of Allium cepa L. 
Fig. 3: Effect of Br-oxph-1 on proliferation/viability of human hepatoma cell line SK-HEP-1; *P ≤ 0.05. 
Synthesis and cytostatic activity of 4-bromo-5-ethyl-2-(ethylamino)- 5-methyl-5H-1,2-oxaphosphole 2-oxide
  • Article
  • Full-text available

January 2018


178 Reads

Synthesis of phosphorus heterocycles has gained increasing interest in recent years. Here we wish to report our results on synthesis and on studying of biological activity of 4-bromo-5-ethyl-2-(ethylamino)-5-methyl-5H-1,2-oxaphosphole 2-oxide (Br-oxph-1) using in vivo and in vitro approaches. Br-oxph-1 represents a structural analogue of 4-bromo-2-(diethylamino)-5-ethyl-5-methyl-5H-1,2-oxaphosphole 2-oxide (Br-oxph). Root growth inhibition test using Triticum aestivum L. seeds was provided in order to determine general toxicity of Br-oxph-1. The effective concentration that cause 50% of root length as compared to control was determined - 8.23 × 10³ μM. Cytotoxic potential of Br-oxph-1 (8.23 × 10³ μM) was evaluated using Allium cepa L.-test. Significant decline in mitotic activity and disturbances of cell cycle kinetics were observed. Further, effects of Br-oxph-1 on human hepatoma cell line SK-HEP-1 in vitro were evaluated by means of cell proliferation assay. The results revealed concentration-dependent and statistically significant inhibitory effect. Concentration of Br-oxph-1 showing 50% reduction in cell proliferation/ viability was 0.642 × 10³ μM. In conclusion, plant test-systems used in this study revealed growth inhibitory and cytostatic effects of Br-oxph-1. Data in vitro was in accordance with these results. Results of present study revealed stronger cytostatic effect of Br-oxph-1 in comparison with Br-oxph. Obviously, modifications in chemical structure of Br-oxph influence its biological effects.

Table 3 : Effects of O. corniculata ethanol extract in the Step down test and step through test
The effect of Oxalis corniculata extract against the behavioral changes induced by 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice

March 2017


365 Reads

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the development of rigidity, resting tremors and postural instability. Recently, the focus of PD's treatment has shifted towards herbal medicines. The aim of the study was to evaluate neuroprotective effect of alcoholic extract of Oxalis corniculata (Oxalidaceae), via the analysis of behavioral features in MPTP (1-methyl,4- phenyl-1,2,3,6-tetra hydro pyridine) mouse model. Behavioral studies were performed by the actophotometer, elevated plus maze, rotarod, hole board, step down and step through tests. Treatment with O. corniculata reversed the alterations in locomotor and muscle coordination in MPTP induced Parkinsonic mouse. The results achieved in this study reveal that different doses of O. corniculata increased memory retention and retrieval significantly. Memory retention and retrieval enhancement by O. corniculata extract could be due to the presence of antioxidants such as flavonoids, coumarins, tocopherols and phenolic acids and their power in scavenge reactive oxygen species.

Table 2 : Antioxidant activity of compounds in the performed assays. 
Evaluation as antioxidant agents of 1,2,4-triazole derivatives: Effects of essential functional groups

January 2015


209 Reads

A series of 1,2,4-triazole derivative compounds substituted with groups of phenol and pyridine were synthesized in high yields and screened against several antioxidant activity parameters such as DPPH, ABTS, metal chelating, reducing power and the total antioxidant activity. The compounds showed better than expected antioxidant activity between the studied biological activity parameters. Among these, compound G(2-(5- mercapto-4H-1,2,4-triazol-3-yl)phenol) had a high total antioxidant activity potential with value of 232.12±6.89 mmol/ml. Also showed fairly good ABTS cation radical and DPPH radical scavenging activity with values of IC50 = 4.59±4.19 and IC50 = 7.12±2.32μg/mL respectively. Further, the antioxidant potential of heterocyclic compounds that 1,2,4-triazole derivatives containing different functional groups were compared with various tests performed and has been shown to increase the activity of electron donating groups. Therefore, the present study demonstrates that phenol and pyridine substituted 1,2,4-triazole compounds would be a better prospective in the development of antioxidant agent.

Synthesis of Some Novel Heterocyclic 1,2,4-triazolo [3,4-b][1,3,4] Thiadiazole Derivatives as Possible Antimicrobial Agents

February 2014


82 Reads

A series of 6-aryl-3-(2,3-dialkoxyphenyl) -[1,2,4]triazole [3,4-b][1,3,4] thiadiazole (7a-7o) were synthesized by condensing 4-amino-5-(2,3-dialkoxyphenyl)-4H-[1,2,4]- triazole-3-thiol (6) with various aromatic carboxylic acids in the presence of phosphorous oxychloride through one-pot reaction. The structures of these newly synthesized compounds were confirmed on the basis of IR, 1H NMR and mass spectral studies. All the synthesized compounds were screened for their antimicrobial activity against a variety of microorganisms.

Efficacy of 5-(2-aroyl)aryloxy methyl-2-phenyl-1,3,4-oxadiazoles as antibacterial and antifungal agents

November 2013


40 Reads

Research and development of potent and effective antimicrobial agents represent one of the most important advances in therapeutics; the main aim of these efforts is not only control the serious infections, but also prevention and treatment of some infectious complications of other therapeutic modalities. A series of 5-(2-aroyl)aryloxy methyl-2-phenyl-1,3,4-oxadiazoles were screened for their antibacterial and antifungal activities. Anti-bacterial activity against B. cereus, S. aureus, B. subtilis, S. aureus (MRSA), E. aerogenes, M. luteus, K. pneumonia, P. aeruginosa, S. typhimurium, E. coli, paratyphi-B, P. vulgaris bacterial strains and anti-fungal activity against C. albicans, A.niger, F.solani, A.flavus, B.cinerea, C.krusei, M. pachydermatis, C.parapsilosis, F.moniliforme, C.gloeosporioides fungal strains were carried out. The bioassays indicated that most of the synthesized compounds showed potential antibacterial and anti-fungal activity.

Synthesis and antimicrobial activity of novel (3,5-dichloro-4-((5-aryl-1,3,4-thiadiazol-2-yl)methoxy) phenyl) aryl methanones

July 2012


44 Reads

A series of novel (3,5-dichloro-4-((5-aryl-1,3,4-thiadiazol-2-yl)methoxy)phenyl) aryl methanones (10a-f), were synthesized by condensing 2-chloromethyl-5-aryl-1,3,4-thiadiazole (9a-c) with aryl(3,5-dichloro-4-hydroxyphenyl) methanones (4a-b) using TBAB and K2CO3. The chemical structure of the newly synthesised compounds was characterized by analytical and spectral (IR, 1H NMR, and LC-MS) methods. The title compounds were screened for qualitative (zone of inhibition) and quantitative antimicrobial activity (MIC) by agar well and microbroth dilution technique, respectively. Among the synthesized compounds in the series, the compound 10f was found to exhibit significant antibacterial activity at lower concentration, against Gram positive bacteria such as Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus and Gram negative bacteria such as E.coli, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumoniae. The rest of the analogues in the series displayed moderate antimicrobial activity when compared to the standard positive controls gentamicin and nystatin.

Review on biological activities of 1,3,4-thiadiazole derivatives

July 2011


458 Reads

The Thiadiazole & their derivatives shown the number of pharmacological activity as anti microbial ,anti inflammatory activity, anti tubercular activity, ant diabetic activity, diuretics, anti depressant & cytotoxic activity. these thiadiazole are the heterocyclic compound which contain the five member ring & nitrogen & sulphur. In this paper we mention the recent derivatives of 1,3,4thiadiazole & their activity.

The analgesic effect of a curcumin analogue 1,5-bis(4'-hydroxy-3'-methoxyphenyl)-1,4-pentadien-3-on (Gamavuton-0) in acute and persistent pain

January 2014


63 Reads

Gamavuton-0 (GVT-0), a curcumin analogue, has been reported to have antiinflammatory and antioxidant activity, however, its analgesic activity has not yet been investigated. This research purpose is to study the effect of GVT-0 on acute and persistent pain using Modified Hot Plate (MHP) method and Formalin test, respectively, on male Swiss mice. In MHP method, the five groups of animals were pretreated with GVT-0 (10, 20, 40, and 80 mg/kg, orally) and indomethacin (4 mg/kgBB, i.p, for positive control), respectively, and immediately followed by stimulation with the carrageenan in sterile saline with a final volume of 50 μl in the left paw. The animals were then placed in hot plate (51oC). The latency time was determined at 90 min post-challenge. In the Formalin test, the six groups of animals were pretreated with GVT-0 (10, 20, 40 and 80 mg/kg, orally), morphine (5 mg/kgBB, i.p), and indomethacin (4 mg/kgBB, i.p) respectively, 60 min prior to the injection of 1.0% aqueous formalin (20 μl) administered by the intraplantar route into the right hindpaw. The licking time was measured at the first 5 min (initial phase, neurogenic) and 10-30 min after formalin injection (late phase, inflammatory). Result showed that GVT-0 has analgesic effect on acute pain using MHP method with ED50 of 27,69 mg/kgBW (p.o). While using Formalin test, GVT-0 showed analgesic activity with ED50 of 109,02 mg/kgBW (p.o) in initial phase, and ED50 of 13,53 mg/kgBW (p.o) in late phase. These results suggest that GVT-0 is a potential candidate for new antiinflammatory and analgesic agent that can be used for the treatment of different painful condition.

Exploring the Synthesis of New 1-(4-Substitutedphenylamino) imidazo[1,5-a]indol-3-one Derivatives as Cyclized Analogs of Leucettines

June 2014


79 Reads

New 1-arylaminoimidazo[1,5-a]indol-3-ones were synthesized as cyclized derivatives of leucettine L41, a low molecular weight inhibitor of the DYRKs/CLKs protein kinases with potential applications in Alzheimer's disease and Down syndrome. In this first approach, access to the desired 1-aminoimidazo[1,5-a]indol-3-ones involved 5 steps and was explored with a series of various primary amines and polar secondary amines in order to introduce molecular diversity on N-1 position. The 5 step synthesis of the 1-arylaminoimidazo[1,5-a]indol-3-ones was achieved and the limiting step of this process was the final cyclization via a sulphur/nitrogen displacement from methylsulfanyl thiourea intermediates. Good results were obtained for isothioureas derived from primary amines. The 1-arylaminoimidazo[1,5-a]indol-3-ones were evaluated on a panel of five protein kinases (DYRK1A, CK1, CDK5/p25, GSK3α/β and CLK1).

Synthesis and characterization of novel 1,6-dihydropyrimidine derivatives for their pharmacological properties

May 2019


81 Reads

The present research work involves the use of commercially available thiophene-2-carbaldehyde as a starting material to construct novel pyrimidine compounds. Synthesis of pyrimidine derivatives has been done by the trimolecular Biginelli condensation reaction, which involves the use of thiophene-2-carbaldehyde with cyano ethylacetate and thiourea to yield 4-oxo-6-(thiophen-2-yl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (1). The intermediate 1 was methylated using methyl iodide and K 2 CO 3 in dimethylformamide (DMF) which afforded dimethylated derivative 1-methyl-2-(methylthio)-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile (2). The intermediate compound 2 when refluxed with hydrazine hydrate in ethanol as a solvent led to the formation of the parent compound 2-hydrazineyl-1-methyl-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile (3), the parent compound 3 was used for the synthesis of carboxamides of N'-(5-cyano-1-methyl-6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidin- 2-yl)substituted benzohydrazide (4a-d) and Schiff bases of (E)-2-(2-substituted benzylidenehydrazineyl)-1-methyl- 6-oxo-4-(thiophen-2-yl)-1,6-dihydropyrimidine-5-carbonitrile (5a-g). Selected title compounds are screened for antibacterial, analgesic, and antifungal activities.

Insights into the structural features of anticancer 1,6-naphthyridines and pyridopyrimidines as VEGFR-2 inhibitors: 3D-QSAR study

October 2020


223 Reads

Vascular endothelial growth factors (VEGFs) mediated VEGFR-2/KDR signaling cascade regulates endothelial cell migration and proliferation. Overexpression of VEGFR-2 has been perceived in different cancers, such as cervical cancer, triple-negative breast cancer, non-small-cell lung carcinoma, hepatocellular carcinoma, thyroid cancer, and renal cell carcinoma. Thus, the inhibition of VEGFR-2 has emerged as an alluring receptor in cancer therapy. The present research work intends to recognize the pharmacophoric features inhibiting VEGFR-2 by using the ligand-based drug design (LBDD) approach for 1,6-naphthyridine and pyridopyrimidine analogues by the 3D-QSAR technique, i.e., comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). 3D-QSAR models were established and validated using training and test set analogues. The alignment of the data set was achieved using the most active analogue (lowest energy conformer) of the series as a template structure. The partial least square analysis for CoMFA and CoMSIA models showed significant ‘leave-one-out’ cross-validation coefficients of 0.659 and 0.689 and the conventional correlation coefficients (r2) of 0.987 and 0.985, respectively. Additionally, bootstrap analysis and cross-validation (leave-half-out method) were used to examine the quality of the generated models and internal reliability within the data set. The predictability of models was evaluated using a test set containing 14 analogues (r2 pred = 0.719 and 0.697). Lastly, the outcomes of the generated models and contour maps were utilized to design the 1,6-naphthyridine and pyridopyrimidine analogues as VEGFR-2 inhibitors.

A new curcumin analog, CCA-1.1, induces cell death and cell cycle arrest in WiDr colon cancer cells via ROS generation

October 2021


36 Reads

The new Pentagamavunone-1 (PGV-1) derivative, chemoprevention-curcumin analog 1.1 (CCA-1.1), is described as an improved physicochemical feature with similar cytotoxic activity on colon cancer cells and binding interaction to various cancer biomarkers. The current study explored the cytotoxic activity related to its ability to promote physiological changes in the WiDr colon cancer cell line. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the cell viability of WiDr and NIH-3T3 cells on the treatment of CCA-1.1 and PGV-1. 2′,7′-dichlorofluorescein diacetate staining, propidium iodide staining, and annexin V-PI staining were conducted to examine reactive oxygen species (ROS) level, cell cycle profiles, and apoptosis, respectively. For more examination on morphological changes, the SA-β-gal staining was used to detect senescence occurrence. We retrieved a more significant cytotoxic effect on WiDr by CCA-1.1 than PGV-1 and no effect on NIH-3T3 fibroblast cells. Our compound stimulated the arrest of the cell cycle at the G2/M phase, apoptosis, ROS generation, and senescence at an equal level to PGV-1. Altogether, these data reinforce CCA-1.1 as a viable alternative to PGV-1, attributed to its improved physicochemical features that are beneficial in designing dosage formulations for medical purposes. © 2021. Febri Wulandari et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (

Purification and Characterization of Extracellular Lipase from Staphylococcus epidermidis (MTCC 10656)

January 2017


92 Reads

Lipases are hydrolytic enzymes with wide range of industrial applications. In the present study Staphylococcus epidermidis strain L2 with ability to produce extracellular lipase enzyme has been isolated from cloth samples collected from the diary industry. The extracellular lipase enzyme has been purified to homogeneity. The purified enzyme has shown a specific activity of 123.95U/mg. The molecular weight of the purified lipase enzyme was found to be 28KDa. The pH and temperature optima of the enzyme were recorded as 7.5 and 40°C respectively. The lipase enzyme has shown stability and activity in presence of varying concentrations of emulsifier and different substrates.

Formulation Development of Solid Dispersions of Bosentan using Gelucire 50/13 and Poloxamer 188

January 2016


244 Reads

The objectives of the present research work are to improve the solubility and dissolution rate of bosentan. Solid dispersions of bosentan were prepared by fusion method by using two selected hydrophilic meltable carriers vis-à-vis gelucire 50/13 and poloxamer 188. Sylysia 350 was used as an adsorbent. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Fourier transform infrared spectra (FT-IR), differential scanning calorimetry (DSC). Solubility studies showed 8 and 10 fold increase in solubility for gelucire 50/13 and poloxamer 188 based solid dispersions respectively. The Gibbs free energy ΔGtr° values were all negative for gelucire 50/13 (0, 0.1, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8 and 10 % w/v) and poloxamer 188 (0, 0.1, 0.25, 0.5, 0.75 and 1 % w/v) indicating spontaneous nature of solubilisation. FT-IR and DSC spectra showed that drug and carriers are compatible with each other. Solid dispersions exhibiting highest solubility were compressed into immediate release tablets by using sodium starch glycolate as superdisintegrant. In vitro dissolution studies, exhibited more than 90 % drug dissolution in 1 h. Gelucire 50/13 and poloxamer 188 plays a significant role in enhancement of drug solubility and dissolution. The adsorbent, sylysia 350 may be used to impart good flow and compressibility to solid dispersions. Among the two carriers, poloxamer 188 exhibited better solubility and dissolution enhancement potential.

Antihyperlipidaemic activity of Spermacoce hispida ethanolic extract in triton WR-1339 induced hyperlipidaemic rats

February 2012


119 Reads

Hyperlipidaemia is the greatest risk factor of coronary heart disease. Currently available hypolipidaemic drugs have been associated with number of side effects. Herbal treatment for hyperlipidaemia has no side effects and is relatively cheap and locally available. Literature claims that Saponins are able to reduce hyperlipidemia. Based on high saponin content in herbal plants, Spermacoce hispida (S. hispida) was selected and the present study focus on the antihyperlipidaemic activity of ethanolic seed extract of S. hispida against triton-WR-1339 induced hyperlipidaemia in rats. Hyperlipidaemia was induced in Wistar rats by intraperitoneal (i.p) injections of Triton WR-1339 at a dose of 400 mg/kg body weight. S. hispida was administered orally at a dose of 200 mg/kg to triton WR-1339 induced hyperlipidaemic rats. After administration of S. hispida shows a significant decrease in the levels of cholesterol, phospholipids, triglycerides, LDL, VLDL and significant increase in the level of HDL in serum and liver tissues against triton induced hyperlipidaemic in rats. Therefore it effectively suppressed the triton induced hyperlipidemia in rats, suggesting the potential protective role in Coronary heart disease.

14, 15-epoxygeranylgeraniol and extracts isolated from Pterodon emarginatus Vog. fruits: antitumor activity on glioblastoma cells

September 2012


33 Reads

Plant-derived substances have traditionally played important roles in the treatment of human diseases, including of great significance to cancer therapy. Plants of the genus Pterodon (Fabaceae, Leguminosae), commonly known as ‘sucupira’, are disseminated throughout the central region of Brazil and have been used frequently in popular medicine. In recent years, interest in these plants has increased considerably. The biological effects of their extracts and pure metabolites have been investigated in several experimental models in vivo and in vitro. Until the present day, the antitumor effect of Pterodon plants on brain tumors is unknown. Therefore, the aim of this work was to investigate the action of P. emarginatus Vogel extracts and its fractions on glioblastoma cells. The hexane (HE), dichloromethane (DE) and ethanol (EE) extracts were obtained from seeds powder in each solvent. The diterpene 14,15-epoxygeranylgeraniol was obtained from HE fractionation. For tumorigenic assays, the extracts and fractions were added to U87MG, a human glioblastoma cells line. The cell viability assay showed that the proliferation of U87MG was inhibited by both extracts and the 14,15-epoxygeranylgeraniol. Further trials in vivo will help to confirm these results, and may contribute to generate natural compounds for the treatment of this type of cancer.

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