Catherina Caballero-George

Acharya Nagarjuna University, Гунтура, Andhra Pradesh, India

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Publications (19)42.52 Total impact

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    ABSTRACT: Fungi occupy an important ecological niche in the marine environment, and marine fungi possess an immense biotechnological potential. This study documents the fungal diversity associated with 39 species of sponges and determines their potential to produce secondary metabolites capable of interacting with mammalian G-protein-coupled receptors involved in blood pressure regulation. Total genomic DNA was extracted from 563 representative fungal strains obtained from marine sponges collected by SCUBA from the Caribbean and the Pacific regions of Panama. A total of 194 operational taxonomic units were found with 58 % represented by singletons based on the internal transcribed spacer (ITS) and partial large subunit (LSU) rDNA regions. Marine sponges were highly dominated by Ascomycota fungi (95.6 %) and represented by two major classes, Sordariomycetes and Dothideomycetes. Rarefaction curves showed no saturation, indicating that further efforts are needed to reveal the entire diversity at this site. Several unique clades were found during phylogenetic analysis with the highest diversity of unique clades in the order Pleosporales. From the 65 cultures tested to determine their in vitro effect on angiotensin and endothelin receptors, the extracts of Fusarium sp. and Phoma sp. blocked the activation of these receptors by more than 50 % of the control and seven others inhibited between 30 and 45 %. Our results indicate that marine sponges from Panama are a "hot spot" of fungal diversity as well as a rich resource for capturing, cataloguing, and assessing the pharmacological potential of substances present in previously undiscovered fungi associated with marine sponges.
    Marine Biotechnology 05/2015; DOI:10.1007/s10126-015-9634-z · 3.15 Impact Factor
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    Nadir Planes, Catherina Caballero-George
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    ABSTRACT: Inhibition of the endothelin system is a recognized therapeutic approach for treating complex cardiovascular diseases. The search for natural inhibitors of the endothelin system has focused mainly on land, with recent, emerging data suggesting the underestimated potential of marine microorganisms for producing leads with cardioprotective potential. The present work reviews natural products identified as inhibitors of the endothelin system, their origin, their mechanism of action, and their ecological significance. Georg Thieme Verlag KG Stuttgart · New York.
    Planta Medica 02/2015; 81(08). DOI:10.1055/s-0034-1396205 · 2.34 Impact Factor
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    ABSTRACT: Angiotensin II and endothelin-1 are potent vasoconstrictive peptides that play a central role in blood pressure regulation. Both peptides exert their pleiotropic effects via binding to their respective G-protein-coupled receptors, i.e., angiotensin AT1 and endothelin type A and type B receptors. In the present study, we have selected six structurally different plant-derived compounds with known cardioprotective properties to evaluate their ability to modulate calcium signaling of the above-mentioned receptors. For this purpose, we used and validated a cellular luminescence-based read-out system in which we measured intracellular calcium signaling in Chinese hamster ovary cells that express the calcium sensitive apo-aequorin protein. Firstly, silibinin, a flavanolignan that occurs in milk thistle (Silybum marianum), was investigated and found to be an antagonist for the human angiotensin AT1 receptor with an affinity constant of about 9 µM, while it had no effect on endothelin type A or type B receptor activation. Quercetin and crocin partially impeded intracellular calcium signaling resulting in a non-receptor-related reduction of the responses recorded for the three investigated G-protein-coupled receptors. Two organosulfur compounds, diallyl disulfide and diallyl trisulfide, as well as the triterpene saponin ginsenoside Rb1 did not affect the activation of the angiotensin AT1 and endothelin type A and type B receptors. In conclusion, we were able, by using a nonradioactive cellular read-out system, to identify a novel pharmacological property of the flavanolignan silibinin. Georg Thieme Verlag KG Stuttgart · New York.
    Planta Medica 12/2014; 81(08). DOI:10.1055/s-0034-1383408 · 2.34 Impact Factor
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    Edgar Marin, Maria Isabel Briceño, Catherina Caballero-George
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    ABSTRACT: Use of biodegradable polymers for biomedical applications has increased in recent decades due to their biocompatibility, biodegradability, flexibility, and minimal side effects. Applications of these materials include creation of skin, blood vessels, cartilage scaffolds, and nanosystems for drug delivery. These biodegradable polymeric nanoparticles enhance properties such as bioavailability and stability, and provide controlled release of bioactive compounds. This review evaluates the classification, synthesis, degradation mechanisms, and biological applications of the biodegradable polymers currently being studied as drug delivery carriers. In addition, the use of nanosystems to solve current drug delivery problems are reviewed.
    International Journal of Nanomedicine 08/2013; 8:3071-91. DOI:10.2147/IJN.S47186 · 4.20 Impact Factor
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    ABSTRACT: Fluorescence correlation spectroscopy and the newly synthesized Alexa532-ET1 were used to study the dynamics of the endothelin ET(A) receptor-ligand complex alone and under the influence of a semisynthetic selective antagonist and a fungal extract on living A10 cells. Dose-dependent increase of inositol phosphate production was seen for Alexa532-ET1, and its binding was reduced to 8% by the selective endothelin ET(A) antagonist BQ-123, confirming the specific binding of Alexa532-ET1 to the endothelin ET(A) receptor. Two different lateral mobilities of the receptor-ligand complexes within the cell membrane were found allowing the discrimination of different states for this complex. BQ-123 showed a strong binding affinity to the "inactive" receptor state characterized by the slow diffusion time constant. A similar effect was observed for the fungal extract, which completely displaced Alexa532-ET1 from its binding to the "inactive" receptor state. These findings suggest that both BQ-123 and the fungal extract act as inverse agonists.
    The Scientific World Journal 05/2012; 2012:524169. DOI:10.1100/2012/524169 · 1.73 Impact Factor
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    Catherina Caballero-George, Mahabir P Gupta
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    ABSTRACT: Panama is a unique terrestrial bridge of extreme biological importance. It is one of the "hot spots" and occupies the fourth place among the 25 most plant-rich countries in the world, with 13.4 % endemic species. Panamanian plants have been screened for a wide range of biological activities: as cytotoxic, brine shrimp-toxic, antiplasmodial, antimicrobial, antiviral, antioxidant, immunosuppressive, and antihypertensive agents. This review concentrates on ethnopharmacological uses of medicinal plants employed by three Amerindian groups of Panama and on selected plants with novel structures and/or interesting bioactive compounds. During the last quarter century, a total of approximately 390 compounds from 86 plants have been isolated, of which 160 are new to the literature. Most of the work reported here has been the result of many international collaborative efforts with scientists worldwide. From the results presented, it is immediately obvious that the Panamanian flora is still an untapped source of new bioactive compounds.
    Planta Medica 06/2011; 77(11):1189-202. DOI:10.1055/s-0030-1271187 · 2.34 Impact Factor
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    ABSTRACT: Fungi represent an essential component of biodiversity not only because of their high species richness at multiple scales, but also because of their ecological, evolutionary and socio-economic significance. Despite poorly understood natural history and uncertain estimates of diversity, marine fungi have been identified as a major source of new natural products with pharmacological applications. The aims of this study were (1) to haracterize fungi associated with marine sponges in protected areas of the Pacific and Caribbean coasts of Panama, and (2) to examine their effects through radioligand binding assays on endothelin ETA (ETA ) and neuropeptide Y Y1 (Y1 ) receptors, which provide an indication of cardioprotective potential. A total of 369 marine sponges were collected in areas of high biodiversity along the Panamanian coasts, including 156 from the western Caribbean and 213 from the eastern Pacific. From these, 2,747 and 2,263 fungal isolates were recovered, respectively, with variable isolation frequencies when sponge fragments were cultivated on five media. After determining the seasonality, geographic stucture, and taxonomic diversity of these fungal assemblages, we identified five strains that inhibited by > 50% the binding of [3H] BQ-123 and one the binding of [3H] neuropeptide Y to the ETA and Y1 receptors, respectively, at 100 µg/ml. Further studies are required to determine whether these interactions are agonistic or antagonistic. Drawing from our methods for solating and screening these fungi we propose a general protocol for capturing, taloguing, and assessing the pharmacological potential of previously undiscovered fungi associated with marine sponges.
    Current Trends in Biotechnology and Pharmacy 01/2010; 4(4):881-889.
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    ABSTRACT: Two new cyclic depsipeptides, 5-OHKF (1) and norKA (2), together with the known congeners kahalalide F (3) and isokahalalide F ((4S)- methylhexanoic kahalalide F) (4) were isolated from the green alga Bryopsis pennata. The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopic analysis and mass spectrometric (ESIMS) data. The absolute configuration of each amino acid of 5-OHKF (1) and norKA (2) was determined by chemical degradation and Marfey's analysis. The biological activities of these two compounds are also reported.
    Journal of Natural Products 11/2009; 72(12):2172-6. DOI:10.1021/np900287e · 3.95 Impact Factor
  • C Caballero-George, T Sorkalla, E Bermingham, H Häberlein
    Planta Medica 07/2008; 74(09). DOI:10.1055/s-0028-1084790 · 2.34 Impact Factor
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    ABSTRACT: The limited international resources for economic aid and conservation can only mitigate poverty and losses of biodiversity. Hence, developing nations must establish the capacity to resolve their problems. Additionally, policy-makers and donors need to obtain scientific input on issues such as global change and ecosystem services. We propose that for nations rich in biodiversity, ecosystem services derived from bioprospecting, or drug discovery, could contribute to economic development. In the case where unstudied samples are shipped abroad for research, the chances of obtaining royalties are infinitesimally small. Therefore developing nations will only realize benefits from bioprospecting through in-country research on their own biodiversity. Policy-makers and donors have failed to appreciate the value of this approach. In order to provide an example of the inherent links between conservation and sustainable economic development, we initiated a drug discovery effort in Panama that emphasizes local benefit. As much of the drug discovery process as possible is conducted in Panamanian laboratories, providing jobs dependent on intact biodiversity and enhancing local research and training. In short, research, plus the spin-offs from research, provide immediate and long-lasting benefits to Panama. The connection between conservation and development has been highlighted in publicity about the project in Panama’s urban media. This provides a constructive alternative to the perception the among the urban populace that economic development inevitably competes with conservation. In summary, our program uses biodiversity to promote human health as well as to support research capacity, economic development and conservation within Panama. The program provides an example of the widely recognized but little developed concept of bioprospecting research as an ecosystem service. KeywordsBioprospecting-Chagas’ disease-Convention on biological diversity-Ecosystem services-ICBG-Leishmaniasis-Malaria-Panama-Policy-makers-Sustainable development
    Biodiversity and Conservation 09/2007; 16(10):2789-2800. DOI:10.1007/s10531-007-9214-2 · 2.07 Impact Factor
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    ABSTRACT: I t is widely recognized that developing countries in the tropics that harbor a large fraction of the world's bio-diversity could, in principle, obtain substantial benefits from their biodiversity. The challenge has been to harness the eco-nomic value of sustainable uses of biodiversity in order to jus-tify the conservation of habitat in its natural state. Promising strategies for meeting this challenge include ecotourism, car-bon credits obtained from intact forest, and ecosystem ser-vices, such as the provision of clean water. Here we focus on how bioprospecting, the investigation of biodiversity as a source of useful medicines or genes (ten Kate and Laird 1999), might, in practice, provide the expected benefits. The Convention on Biological Diversity (1992–1993) and more recent agreements recognize that nations have owner-ship of, and can control access to, species ("genetic resources") within their boundaries; these agreements mandate equi-table sharing of the benefits derived from biodiversity (Gollin 1993, 1999). A principal focus has been on the legal issues con-cerning bioprospecting, such as the definition of prior in-formed consent for the use of traditional knowledge and specification of benefit-sharing arrangements (Blaustein 2006, CBD 2006). This emphasis resulted from the many cases—some recent—of the use of biodiversity without rec-ompense, as occurred with the insecticide from the Indian tree Azadirachta indica (neem), which has low toxicity to verte-brates, and with a heat-stable enzyme from the bacterium Thermus aquaticus, which is a key research tool. As a con-sequence, many governments have inhibited basic research on biodiversity (Grajal 1999, Gómez-Pompa 2004). It is very likely that biodiversity-based research carried out by phar-maceutical and agricultural companies also has been inhib-ited, although the extent of this inhibition is difficult to quantify. Even though bioprospecting research could promote substantial economic growth in areas with high biological diversity, such as the tropics, countries there have failed to capture the value of their biodiversity.
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    ABSTRACT: Bioprospecting has frequently been cited as a sustainable use of biodiversity. Nevertheless, the level of bioprospecting in biodiversity-rich tropical regions falls below its potential, with the result that bioprospecting has produced only limited economic benefits. We present a bioprospecting program that, in addition to promoting drug discovery, provides economic benefits to and promotes conservation in Panama through the sustainable use of biodiversity. The program was initiated using insights from 20 years of nonapplied ecological research to enhance the likelihood of finding treatments for human disease. Samples are not sent abroad; rather, most of the research is carried out in Panamanian laboratories. Panama has received immediate benefits for the use of its biodiversity in the form of research funding derived from sources outside Panama, training for young Panamanian scientists, and enhanced laboratory infrastructure. Over the long term, discoveries derived from bioprospecting may help to establish research-based industries in Panama.
    BioScience 11/2006; DOI:10.1641/0006-3568(2006)56[1005:SEBAPC]2.0.CO;2 · 5.44 Impact Factor
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    ABSTRACT: Different types of triterpenes including saponins and aglycons were evaluated for their ability to inhibit [3H] BQ-123 and [3H] angiotensin II binding to the human endothelin 1 ETA and angiotensin II AT1 receptors, respectively. Selectivity for only one of the two receptors was exhibited by asiatic acid and its saponins (ETA) and oleanolic acid (AT1). To a lesser extent betulinic acid, beta-amyrin and friedelin also showed selectivity for the ETA receptor. To address the question whether the effect of saponins on cell membranes might interfere with the normal binding of specific radioligands to their receptors, the activity of saponins with different haemolytic properties were compared. Highly haemolytic saponins such as alpha-hederin and beta-escine showed partial (60%) inhibition of radioligand-binding to the ETA receptor and complete inhibition (100%) to the AT1 receptor. Moreover, the haemolytically inactive kryptoescine, at the same concentration, caused complete inhibiton of radioligand-binding to both receptors, indicating that inhibition of receptor binding was not related to the membrane-interacting properties of saponins.
    Phytotherapy Research 09/2004; 18(9):729-36. DOI:10.1002/ptr.1521 · 2.40 Impact Factor
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    ABSTRACT: The type of interaction of 5-methyl-2,3,7,8-bis(methylenedioxy)benzo[c]phenanthridinium (sanguinarine), an alkaloid isolated from the root of Bocconia frutescens L., with the human angiotensin AT(1) receptor was evaluated in both intact cells and membrane binding of [3H](2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic acid) ([3H]candesartan). The results indicate that the inhibition of [3H]candesartan binding by sanguinarine is independent of cell viability, since the alkaloid inhibited at a similar extent radioligand binding on both intact Chinese hamster ovary (CHO) cells transfected with the human angiotensin AT(1) receptor (hAT(1)) and their cell membranes (K(i)=0.14 and 1.10 microM, respectively). The unsuccessful recovery of [3H]candesartan binding after washing sanguinarine off the cells suggested a nearly irreversible or slow reversible interaction. Saturation binding studies showed a substantial reduction of the B(max) without affecting the K(d). In addition, the presence of 2-n-butyl-4chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole (losartan) could not prevent sanguinarine inhibition of [3H]candesartan binding neither. The present findings indicate that sanguinarine interacts with the receptor in a slow, nearly irreversible and noncompetitive manner.
    European Journal of Pharmacology 02/2003; 458(3):257-62. DOI:10.1016/S0014-2999(02)02819-4 · 2.68 Impact Factor
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    ABSTRACT: A bioassay-guided fractionation of the 70% acetone extract of the bark of Guazuma ulmifolia Lam. on the inhibition of angiotensin II binding to the AT 1 receptor led to the isolation and identification of bioactive oligomeric and polymeric proanthocyanidins consisting mainly of (-)-epicatechin units. The displacement of [3H]-angiotensin II binding was dose-dependent and correlated with the degree of polymerization of the different fractions containing proanthocyanidins. A strong displacement was seen for the residual fraction suggesting that the most active substances corresponding to the highly polymerized proanthocyanidins. Angiotensin II AT 1 receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins.
    Planta Medica 01/2003; 68(12):1066-71. DOI:10.1055/s-2002-36344 · 2.34 Impact Factor
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    ABSTRACT: A bioassay-guided fractionation of the 70% acetone extract of the bark of Guazuma ulmifolia Lam. on the inhibition of angiotensin II binding to the AT 1 receptor led to the isolation and identification of bioactive oligomeric and polymeric proanthocyanidins consisting mainly of (-)-epicatechin units. The displacement of [3H]-angiotensin II binding was dose-dependent and correlated with the degree of polymerization of the different fractions containing proanthocyanidins. A strong displacement was seen for the residual fraction suggesting that the most active substances corresponding to the highly polymerized proanthocyanidins. Angiotensin II AT 1 receptor binding might be considered as a potentially interesting biological activity of proanthocyanidins contributing to the very broad spectrum of biological activities of the condensed tannins
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    ABSTRACT: A bioassay-guided fractionation of the 80 % ethanolic extract from Bocconia frutescens L. roots, showing a dose-dependent inhibitory effect towards both [(3)H]-angiotensin II and [(3)H]-BQ-123 binding to the human angiotensin II AT 1 and endothelin 1 ET(A) receptors, led to an alkaloidal subfraction as the only responsible fraction for the activity of the whole extract. Among the alkaloids present in this fraction sanguinarine and chelerythrine were significant inhibitors of [(3)H]-angiotensin II binding (hAT 1 receptor), with IC(50) values within the micromolar range. On the contrary, the [(3)H]-BQ-123 binding (ET(A) receptor) was only weakly inhibited. Moreover, other members of the isoquinoline alkaloid family such as chelidonine and some protoberberine alkaloids exhibited no affinity for the two receptors. The present work shows the possible structure-activity relationship for these benzophenanthridine alkaloids on a screening bioassay using both stably transfected Chinese hamster ovary (CHO) and the human neuroblastoma SK-N-MC cells. Furthermore, the ability of these compounds to block AT(1) and/or ET(A) receptors may provide some justification for the traditional use of Bocconia frutescens L. to control hypertension.
    Planta Medica 10/2002; 68(9):770-5. DOI:10.1055/s-2002-34406 · 2.34 Impact Factor
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    ABSTRACT: Nineteen plants from the Republic of Panama were selected by their traditional uses in the treatment of hypertension, cardiovascular, mental and feeding disorders and 149 extracts were screened using radioligand-receptor-binding assays. The methanol:dicloromethane extracts of the bark and leaves of Anacardium occidentale L., the leaves of Begonia urophylla Hook., the roots of Bocconia frutescens L., the stems and leaves of Cecropia cf.obtusifolia Bertol., the branches of Clusia coclensis Standl., the bark of Cochlospermum vitifolium (Willd.)Spreng., the roots of Dimerocostus strobilaceus Kuntze, the bark of Guazuma ulmifolia Lam., the leaves of Persea americana Mill. and the branches of Witheringia solanaceae L'Her. inhibited the [3H]-AT II binding (angiotensin II AT1 receptor) more than 50%. Only extracts of the roots of Dimerocostus strobilaceus Kuntze and the stems of Psychotria elata (Sw.) Hammel were potent inhibitors of the [3H] NPY binding (neuropeptide Y Y1 receptor) more than 50% and the ethanolic extracts of the leaves of Cecropia cf. obtusifolia Bertol., the leaves of Hedyosmum bonplandianum H.B.K., the roots of Bocconia frutescens L., the stem of Cecropia cf. obtusifolia Bertol. and the branches of Psychotria elata (Sw.) Hammel showed high inhibition of the [3H] BQ-123 binding (endothelin-1 ET(A) receptor) in a preliminary screening. These results promote the further investigation of these plants using the same assays.
    Phytomedicine 02/2001; 8(1):59-70. DOI:10.1078/0944-7113-00011 · 2.88 Impact Factor

Publication Stats

141 Citations
42.52 Total Impact Points

Institutions

  • 2013
    • Acharya Nagarjuna University
      • Department of Biotechnology
      Гунтура, Andhra Pradesh, India
  • 2007–2012
    • Smithsonian Tropical Research Institute
      Ciudad de Panamá, Panamá, Panama
  • 2011
    • Universidad de Panamá
      Chitré, Herrera, Panama
  • 2009
    • University of Mississippi
      Mississippi, United States
  • 2001–2004
    • University of Antwerp
      • Department of Pharmaceutical sciences
      Antwerpen, Flemish, Belgium
  • 2002–2003
    • Vrije Universiteit Brussel
      Bruxelles, Brussels Capital, Belgium