scholarly journals Parallelism of Chemicostructural Properties between Filgrastim Originator and Three of Its Biosimilar Drugs

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Alessandra Gianoncelli ◽  
Michela Bertuzzi ◽  
Michela Guarienti ◽  
Sara Vezzoli ◽  
Sara Anna Bonini ◽  
...  
Keyword(s):  
Biological Activity ◽  
Reference Product ◽  
Biological Activities ◽  
Chemical Characterization ◽  
Structural Similarity ◽  
Functional Assay ◽  
Biological Drugs ◽  
Reference Drug ◽  
Rp Hplc

The approval and granting of marketing authorization for a putative biosimilar is based on strong comparability studies with its biological reference product. This is due to the complexity of the structure and nature of the manufacturing process of biological drugs. Hence, a rigorous analytical workflow for chemical characterization and clinical trials to evaluate the efficacy and safety is required to demonstrate their high similarities to the reference drug. This work is focused on the comparison of the originator of filgrastim with three of its biosimilars by evaluating their structural similarity and biological activity. Qualiquantitative analyses were performed by MALDI-TOF/TOF-MS and RP-HPLC-UV. An innovative functional assay using zebrafish as the animal model was developed to evaluate the biological activities of the drugs. The different analyses performed in this study highlighted the structural similarity of biosimilar drugs and their originator. This result was further confirmed by a similar in vivo biological activity.

scholarly journals Biological activities of recombinant chicken leptin C4S analog compared with unmodified leptins

2000 ◽  
Vol 279 (1) ◽  
pp. E116-E123 ◽  
Author(s):  
S. Dridi ◽  
N. Raver ◽  
E. E. Gussakovsky ◽  
M. Derouet ◽  
M. Picard ◽  
...  
Keyword(s):  
Biological Activity ◽  
Food Intake ◽  
Leptin Receptor ◽  
Biological Activities ◽  
Wild Type ◽  
Escherichia Coli Cells ◽  
Prokaryotic Expression Vector ◽  
Long Form

The chicken leptin sequence, in contrast to mammalian leptins, contains an unpaired Cys at position 3 of the original cDNA ( AF012727 ). The presence of an extra Cys may confer a different structure and affect the leptin's biological activity. To address this, we studied the effects of wild-type and mutated (C4S) chicken leptins in vitro and in vivo and compared them with mammalian leptin prepared from ovine leptin cDNA. The prokaryotic expression vector pMON, encoding full-size A(−1) chicken leptin ( AF012727 ), was mutated using a mutagenesis kit, yielding the C4S analog. Escherichia coli cells transformed with this vector overexpressed large amounts of chicken leptin C4S upon induction with nalidixic acid. The expressed protein, found in the inclusion bodies, was refolded and purified to homogeneity on a Q-Sepharose column, yielding three electrophoretically pure fractions, eluted from the column by 100, 125, and 150 mM NaCl, respectively. All three fractions showed a single band of the expected molecular mass (16 kDa) and were composed of >95% monomeric protein. Proper refolding was evidenced by comparing the circular dichroism spectrum of the analog with spectra of nonmutated chicken and ovine leptins. The biological activity of the C4S analog was evidenced by its ability to stimulate proliferation of leptin-sensitive BAF/3 cells transfected with a long form of human leptin receptor construct similar to its nonmutated counterpart, indicating that Cys4 plays no role in leptin activity. The in vitro activity of both wild-type and mutated chicken leptins was ∼10-fold lower than that of ovine leptin. After intravenous or intraperitoneal injections, C4S analog and the nonmutated chicken and ovine leptins all lowered the food intake of starved 9-day-old broiler or 5-wk-old layer male chickens by 11–34%. Monitoring food behavior revealed that the attenuated food intake resulted not from a decreased number of approaches to the feeders but from a decrease in the average time spent eating during each approach.

Progress and development of C-3, C-6, and N-9 position substituted carbazole integrated molecular hybrid molecules as potential anticancer agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Pratibha Mehta Luthra ◽  
Nitin Kumar
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Structural Motif ◽  
Hybrid Compounds ◽  
Hybrid Molecules ◽  
Anticancer Mechanism ◽  
Pharmacologically Active

Abstract: The carbazole skeleton, a key structural motif occurring naturally or chemically synthesized, have shown various biological activities. Molecular hybridization based on the combination of two or more bioactive pharmacophores has been an important tool to convert the potent structural leads to form new hybrid compounds with improved biological activity. In recent years, modifications/substitutions of the carbazole motif at C3, C6, N9 position have been carried to develop novel carbazole based potential anticancer agents in the cancer therapy. In the last fifteen years, several compounds based on carbazole core integrated to pharmacologically active molecular hybrid having active pharmacophore such as 1,3,4-thiadiazole, thiazole, guanidine, sulfonamides, glyoxamides, imidazole, phenanthrene, rhodamine, chalcones, imidazopyridine, platinum 2H-chromen-2-one, hydrazones, piperazine, Isoxazole-thiadiazole, pyrazole etc. have been synthesized showing anticancer profile at sub-micromolar to nano-molar concentrations. We have thoroughly reviewed the design, progress and development of C-3, C-6, and N-9 position substituted carbazole derivatives integrated with various medicinally active pharmacophore as potential anticancer agents evaluated against various cancer cell lines. Additionally, the anticancer mechanism and in vivo activity of the reported compounds have been discussed. This study will support in designing of a new pharmacophore that can be linked to carbazole motif for development for new, potent and target specific anticancer drugs with improved pharmacokinetics and minimal side effects.

scholarly journals Ethnopharmacology, Phytochemistry, and Pharmacological Properties of Thymus satureioides Coss.

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Naoufal El Hachlafi ◽  
Abderrahim Chebat ◽  
Kawtar Fikri-Benbrahim
Keyword(s):  
Essential Oils ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Chemical Characterization ◽  
Pharmacokinetic Studies ◽  
Pharmacological Studies ◽  
Thymus Satureioides

Thymus satureioides Coss. (Lamiaceae) is a Moroccan medicinal plant locally known as “Azkouni” or “Zaitra.” It is widely used in traditional medicine to treat various ailments, including hypertension, diabetes, cold, fever, dermatological and circulatory disorders, immune problems, bronchitis, nociception, cooling, pharyngitis, cough, and influenza. The current review aims to critically summarize the literature on ethnopharmacological uses, chemical profile, and pharmacological investigations of T. satureioides in order to provide data support and scientific evidences for further investigations. Electronic databases such as Scopus, PubMed, Web of Science, SciFinder, ScienceDirect, Google Scholar, and Medline were used to gather data on T. satureioides. Chemical characterization of T. satureioides essential oils (EOs) and extracts allowed to identify a total of 139 bioactive compounds, mainly belonging to the terpenoids, phenolic acids, and flavonoids classes. T. satureioides especially its essential oils exhibited numerous biological activities such as antibacterial, antifungal, anti-inflammatory, antioxidant, antidiabetic, anticancer, antiparasitic, and hypolipedemic activities. In light of these findings, further studies to transmute the traditional application of T. satureioides into scientific-based information are strongly required. Additional in vivo pharmacological studies are recommended to validate the results of the in vitro studies. Moreover, comprehensive preclinical and clinical trials on the pharmacological mechanisms of action of this plant and its bioactive compounds on molecular targets should be performed. Finally, more efforts must be focused on toxicological assessments and pharmacokinetic studies, in order to ensure the safety and the efficiency of T. satureioides.

scholarly journals Peptide fragments of bradykinin show unexpected biological activity not mediated by B1 or B2 receptors

2021 ◽  
Author(s):  
Igor Souza-Silva ◽  
Cristiane de Paula ◽  
Lucas Bolais-Ramos ◽  
Anderson Santos ◽  
Filipe da Silva ◽  
...  
Keyword(s):  
Biological Activity ◽  
Adult Male ◽  
Wistar Rats ◽  
Vascular Reactivity ◽  
Biological Activities ◽  
No Production ◽  
Peptide Fragments ◽  
Kinin System ◽  
Male Wistar Rats

Background and purpose: Bradykinin [BK-(1-9)] is an endogenous nonapeptide involved in multiple physiological and pathological processes. A long-held belief is that peptide fragments of BK-(1-9) are biologically inactive. Here, we have tested the biological activities of BK-(1-9) and two major peptide fragments in human and animal systems. Experimental Approach: Levels of BK peptides in male Wistar rat plasma were quantified by mass spectrometric methods. Nitric oxide was quantified in human, mouse and rat cells, and loaded with DAF-FM. We used aortic rings from adult male Wistar rats to test vascular reactivity. Changes in blood pressure and heart rate were measured in conscious adult male Wistar rats. Key results: Plasma levels of BK-(1-7) and BK-(1-5) in rats were increased following infusion of BK-(1-9). All tested peptides induced NO production in all cell types tested. However, unlike BK-(1-9), NO production elicited by BK-(1-7) or BK-(1-5) was not inhibited by B or B receptor antagonists. BK-(1-7) or BK-(1-5) also induced concentration-dependent vasorelaxation of aortic rings, without involving B or B receptors. In vivo, either intravenous or intra-arterial administration of BK-(1-7) or BK-(1-5) induced similar hypotension response. Conclusions and implications: BK-(1-7) and BK-(1-5) are endogenous peptides present in plasma. They are formed, at least partially, through the BK-(1-9) proteolysis. BK-related peptide fragments show biological activity, not mediated by B or B receptors. These BK-fragments could constitute new, active components of the kallikrein-kinin system.

MODEL STUDIES IN VITRO WITH LONG-ACTING HORMONAL PREPARATIONS

1970 ◽  
Vol 64 (4) ◽  
pp. 656-669 ◽  
Author(s):  
J. van der Vies
Keyword(s):  
Biological Activity ◽  
Active Component ◽  
Biological Activities ◽  
Pharmacological Properties ◽  
Model Studies ◽  
Rate Of Absorption ◽  
Long Acting ◽  
Hydrolysis Of

ABSTRACT Since the biological activities of long-acting hormonal preparations, containing steroids or esters of steroids dissolved in arachis oil, depend very much on the rate of absorption from the intramuscular depot, an in vitro model for the latter has been developed. In this model the solution of the drug in oil is applied to a strip of filter paper and the spot eluted with a stream of hog plasma. Using this model, results were obtained which correlated with the observed rates of resorption in vivo. This demonstrates that the physical process underlying parenteral resorption depends on the distribution of the steroid between oil and plasma. As far as these esters of steroids are concerned, the steroid moiety of which is the ultimate active component, the hydrolysis of the ester by the esterase of the transporting plasma is another important factor. This has been studied in an in vitro system. The results obtained with both models proved valuable in understanding the pharmacological properties of a number of anabolic, androgenic and progestational steroids and steroid esters and also in explaining the differences in biological activity between closely related preparations.

Some biological activities of cronolone and medroxyprogesterone acetate in the uterus of the sheep, mouse and rabbit

1989 ◽  
Vol 1 (2) ◽  
pp. 157 ◽  
Author(s):  
X Zhang ◽  
BG Miller
Keyword(s):  
Biological Activity ◽  
Medroxyprogesterone Acetate ◽  
Biological Activities ◽  
Decidual Cell ◽  
Cell Reaction ◽  
Limited Growth ◽  
Mouse Uterus ◽  
Breeding Activity ◽  
Ovariectomized Mice

Cronolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-acetoxypregn-4-ene-3,20-dione) is widely employed to regulate breeding activity in the ewe, but its biological activity in the uterus of this and most other species has not been studied. In this study several in vivo uterus-related activities of cronolone have been examined in the sheep, mouse and rabbit. In some experiments the corresponding activities of medroxyprogesterone acetate (6 alpha-methyl-17 alpha-acetoxypregn-4-ene-3,20-dione, MAP) were also examined. Cronolone maintained pregnancy in ovariectomized ewes but not in ovariectomized mice and rabbits; it terminated pregnancy in some mice and in all rabbits that were receiving daily progesterone treatment. Cronolone could not sensitize the mouse uterus for the induction of the decidual-cell reaction or block the induction of such sensitivity by progesterone, but did support limited growth of the oil-stimulated horn after sensitization with progesterone. Cronolone induced uteroglobin secretion by rabbit endometrium. It was concluded that, whereas MAP is a potent progestogen in the sheep, mouse and rabbit, cronolone is a progestogen in the sheep and rabbit only. In the mouse and especially the rabbit, cronolone has other, non-progestational activities, which block pregnancy.

scholarly journals Influence of Mikania laevigata Extract over the Genotoxicity Induced by Alkylating Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Daliane Medeiros Mazzorana ◽  
Vanessa Nicolau ◽  
Jeverson Moreira ◽  
Patrícia de Aguiar Amaral ◽  
Vanessa Moraes de Andrade
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Alkylating Agents ◽  
Damage Index ◽  
Methyl Methanesulfonate ◽  
Native Plant ◽  
Mikania Laevigata ◽  
Respiratory Complaints ◽  
Plant Compounds

Medicinal plants are still widely used worldwide; yet for some species, little or no information is available concerning their biological activity, specially their genotoxic and antimutagenic potential. Mikania laevigata (Asteraceae) is a native plant from South America, and its extracts are largely used to treat respiratory complaints. The aim of the present work was then to evaluate, in vivo, the potential biological activity of M. laevigata on the genotoxicity induced by methyl methanesulfonate (MMS) and cyclophosphamide (CP), using the comet assay. Male CF1 mice were divided into groups of 5-6 animals, received by gavage 0.1 mL/10 g body wt of water, Mikania laevigata extract (MLE), MMS, and CP. Results showed that treatment with 200 mg/kg of the MLE previously to MMS and CP administration, respectively, reduced the damage index (DI) in 52% and 60%, when compared to DI at 24 h. Pretreatment also reduced the damage frequency (DF) in 56% (MMS) and 58% (CP), compared to DF at 24 h. MLE administration has been shown to protect mouse DNA from damage induced by alkylating agents; this corroborates to the biological activities of M. laevigata and points towards the need of plant compounds isolation to proceed with further studies.

Solid phase synthesis and biological activities of oxytocin carba analogues containing threonine in position 4

1985 ◽  
Vol 50 (2) ◽  
pp. 418-427 ◽  
Author(s):  
Michal Lebl ◽  
Victor J. Hruby ◽  
Jiřina Slaninová ◽  
Tomislav Barth
Keyword(s):  
Biological Activity ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Activities ◽  
High Biological Activity ◽  
Phase Synthesis

Solis phase methodology was developed for the synthesis of carba-analogues of oxytocin. Two known compounds (deamino-1-carba-oxytocin (I) and deamino-6-carba-oxytocin (II)) and two new analogues ([4-threonine]deamino-1-carba-oxytocin (III) and [4-threonine]deamino-6-carba-oxytocin (IV)) were synthesized using different approaches. The latter two compounds were found to possess high biological activity in the rat uterotonic (in vitro and in vivo) and galactogogic (in vivo) assays.

scholarly journals PREDICTION OF ACTIVITY SPECTRA OF SUBSTANCES ASSISTED PREDICTION OF BIOLOGICAL ACTIVITY SPECTRA OF POTENTIAL ANTI-ALZHEIMER’S PHYTOCONSTITUENTS

2017 ◽  
Vol 10 (16) ◽  
pp. 13
Author(s):  
Abhinav Anand ◽  
Neha Sharma ◽  
Navneet Khurana
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
The Other ◽  
Pharmacological Intervention ◽  
Input Line ◽  
In Vivo Evaluation ◽  
Other Hand ◽  
Better Than

Objective: To predict the biological activity of certain phytoconstituents for their anti-AD effects.Methods: Several phytoconstituents were selected on the basis of reported literature. The anti-AD activities of selected phytoconstituents were predicted by employing canonical simplified molecular-input line-entry system obtained from PubChem using PASS online.Results: Several phytoconstituents were predicted to have effects better than marketed drugs under some or the other out of the chosen six areas of pharmacological intervention. On the other hand, several new avenues were predicted in which the in vitro and in vivo evaluation of the phytoconstituents can be made on the basis of PASS predicted activities.Conclusion: PASS is an important tool for virtually screening the compounds of interest for the biological activities of interest. This helps the researchers to streamline the research. However, PASS has its own share of limitations amidst a multitude of merits.

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