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INBIOAR  WE DISCOVER


UNA EMPRESA  DEL GRUPO  ROSENTAL


WE INNOVATE IN NATURAL PRODUCTS FOR CROP PROTECTIONS.

WHO WE ARE

Maria Lucia Travaini

She is a biotechnologist with a Ph. D. in biological sciences from the National University of Rosario, School of Biochemical and Pharmaceutical Sciences with experience in bioactive natural products and plant biology. She contributed to the development of the method to search for, evaluate, and select plant extracts with promising phytotoxic activity. Now she is working in R&D+i and in the scaling up.

Gustavo Sosa

He is a forest engineer from the National University of Santiago del Estero and has a Ph. D. in biochemistry from the National University of Rosario, School of Biochemical and Pharmaceutical Sciences. He is an entrepreneur in biological sciences and plant technology. After a period of post docs in the US, he started different companies in Argentina. He founded INBIOAR in 2010 with capital partners. He teaches plant biochemistry and is a consultant and lecturer of technological Startups.

In INBIOAR we encourage interdisciplinary joint work among scientists and companies from different regions.

Collaborators

Helmut Walter


He is an agronomist with a Ph.D. (Dr. sc. agr.) in agricultural sciences/weed science from the University of Hohenheim, Germany. As visiting scientist with the USDA in Texas, he worked on remote sensing related topics. Consultancies on weed problems in production systems brought him to various countries in Africa, Asia and the Middle East. In 2003, the WSSA elected him as Honorary Member for his contributions to weed science.

A few years ago, he retired from BASF, where for more than 25 years he had been responsible for the discovery and development of new herbicides. Via his AgroField Consulting business he is currently supporting various projects related to crop protection.
His mentoring and partnership based on his experience in the global crop protection industry have been and continue to be key to INBIOAR.

Mentors & Partners

Lisandro Rosental

Lisandro is the partner and CEO of “Rosental Inversiones”. ROSENTAL is a leading firm with interests in industries involving areas such as agriculture, real estate, hotel management, food and technology, and its consolidated foundation in the financing area. Lisandro is partner of INBIOAR and he gives permanent support to the strategy and business development of the company as well as a source of regular consultancy.

Federico Ortega

He is an accountant, he did his MBA at IESE, Barcelona and Rotterdam School of Management. He is dedicated to finance and leading different kind of projects. As an entrepreneur, he leaded a setting up of an emergency medicine business. Additionally, he leaded many real estate business projects. His experience in INBIOAR supports the strategy and the vision of the company. Federico is partner of the company and a business developer.

Sebastian Azerrad

He is a lawyer dedicate to business law. He supports companies dealing with startups, contracts, project finance and the day to day business development. Sebastian´s support to INBIOAR has been very helpful since the beginning focusing in the setup of the company, the advice in many agreements as well as the business strategy of the same.

 

WHAT  WE  DO

INBIOAR

Biological Research in Agrochemicals, from Rosario City, Argentina.

INBIOAR S.A. is a Startup dealing with the Agri Drug Discovery area. Since 2010, we are dedicated to the discovery of new active ingredients and products for agroindustry from plant natural compounds or extracts. 


We screen large areas collecting plant samples and soil to determine later in the lab the presence of herbicides. We first ask for the authorization of the Flora and Fauna State office to collect and study plant species. We later cultivate the species to produce the plant material.


We have developed a systematic process or method to search for, evaluate and select plant extracts with promising herbicidal activity. During 2010-2012, we collected 2400 samples. After a selection process, we found 27 aqueous extracts that were phytotoxic to different weeds.

From the best extracts, we purify the active molecules and, if possible, we file a patent to protect that discovery. Beside our effort to purify compounds, we found that very active plant extracts work very well by themselves as herbicides.


Over these years, we have accumulated a valuable expertise in research and technology transfer in the area of herbicides and bio-herbicides. 

This allows us to offer our services to local and global companies interested in innovation and development of new products for crop protection using the wild flora of their countries or regions.

Natural compounds many times are useful as leads for future work in the lab to produce more bioactive molecules. We have not develop this area yet, but we have in mind to do it the future.


We have learned where and when to collect the material. Interesting plants with herbicidal activity are not possible to find in all regions. The same plant species growing in different areas may produce different amount of inhibitors. We found out which particular characteristics must include a region to support a vegetation with higher chances to produce interesting plants to our project.


Apart from Argentina, we have detected many regions of interest to our project in USA, Paraguay, Uruguay, Perú, Mexico, Colombia, India and the Sub Sahara semi-desert region. We plan to establish joint ventures with companies in those countries to collect samples and produce “in house” the natural plant extracts.

As a summary, we are able to screen large areas and select the best plant extracts with herbicidal activity. Then we can work with both, the most bioactive plant extracts or the pure active molecules, for future formulations. To complete the process, we transfer our expertise to the companies so that they can produce commercial products.

OUR  WORK

Herbicidal Composition comprising Chromone Derivatives and Method for Weed Control.
Inventores: Gustavo SOSA; M. Lucía TRAVAINI; Néstor CARRILLO; Eduardo CECCARELLI; Helmut WALTER. Submitted to the PCT. (2016) N/Ref: 639-3033 PCT.


Khellin and Visnagin, Furanochromones from Ammi visnaga (L.) Lam., as Potential Bioherbicides.

Maria L. Travaini, Gustavo M. Sosa, Eduardo A. Ceccarelli, Helmut Walter, Charles L. Cantrell, Néstor J. Carrillo, Franck E. Dayan, Kumudini M. Meepagala, and Stephen O. Duke. Journal of Agricultural and Food Chemistry, 2016, 64 (50), pp 9475–9487.

Plants constitute a source of novel phytotoxic compounds to be explored in searching for effective and environmentally safe herbicides. From a previous screening of plant extracts for their phytotoxicity, a dichloromethane extract of Ammi visnaga (L.) Lam. was selected for further study. Phytotoxicity-guided fractionation of this extract yielded two furanochromones: khellin and visnagin, whose herbicidal activity had not been described before. Khellin and visnagin were phytotoxic to model species lettuce (Lactuca sativa) and duckweed (Lemna paucicostata), with IC50 values ranging from 110 to 175 μM. These compounds, also inhibited the growth and germination of a diverse group of weeds at 0.5 and 1 mM. These weeds included five grasses [ryegrass (Lolium multiflorum), barnyardgrass (Echinocloa crus-galli), crabgrass (Digitaria sanguinalis), foxtail (Setaria italica), and millet (Panicum sp.)] and two broadleaf species [morningglory (Ipomea sp.) and velvetleaf (Abutilon theophrasti)]. During greenhouse studies visnagin was the most active and showed significant contact postemergence herbicidal activity on velvetleaf and crabgrass at 2 kg a. i. ha-1. Moreover, its effect at 4 kg a. i. ha-1 was comparable to the bioherbicide pelargonic acid at the same rate. The mode of action of khellin and visnagin was not a light-dependent process. Both compounds caused membrane destabilization, photosynthetic efficiency reduction, inhibition of cell division and cell death. These results support the potential of visnagin, and possibly khellin, as bioherbicides or lead molecules for the development of new herbicides.


Herbicidal Composition comprising Chromone Derivatives and Method for Weed Control.

Inventores: Gustavo SOSA; M. Lucía TRAVAINI; Néstor CARRILLO; Eduardo CECCARELLI; Helmut WALTER; Stephen DUKE; Charles CANTREL; Kumudini MEEPAGALA (2015) Provisional patent in USA 62/272.880. N/Ref.: 577 US PROV.


Khellin and visnagin, furanochromones from Ammi visnaga (L.) Lam., as potential bioherbicides.

M. L. Travaini, N. J. Carrillo, E. A. Ceccarelli, H. Walter, G. M. Sosa, C. L. Cantrell, K. M. Meepagala, S. O. Duke. 56th Meeting of the Weed Science Society of America (WSSA) and 69th Meeting of the Southern Weed Science Society (SWSS) (2016) San Juan, Puerto Rico.

There is an increasing demand of new molecules that serve as leads structures for the development of herbicides. Plants natural products provide an attractive alternative in finding effective and environmentally safe phytotoxic compounds, with high structural diversity and novel modes of action. Considering this situation, a systematic process of searching, evaluation and selection was developed in order to find plant extracts with promising phytotoxic activity.
As a result of this screening process involving nearly 2400 plant extracts from different regions of Argentina, a dichloromethane extract of toothpick weed (Ammi visnaga (L.) Lam.) was selected because of its significant herbicidal activity. Phytotoxicity assay-guided fractionation yielded two furanochromones: khellin and visnagin. These compounds have been previously reported in toothpick weed, but their herbicidal activity has not been described before.
Khellin and visnagin significantly inhibited the development of lettuce (Lactuca sativa) (germination IC50 = 700 and 740 μM, growth IC50 = 110 and 170 μM) and duckweed (Lemna paucicostata) (growth IC50 = 160 and 120 μM). Also, during laboratory bioassays in Petri dishes, both compounds at 1 mM strongly interfered with growth and germination of weeds: ryegrass (Lolium perenne), morningglory (Ipomea sp.), foxtail (Setaria italica) and millet (Panicum sp.). The natural compounds’ inhibitory effects were similar to those caused by acetochlor (0.54 mM) and glyphosate (0.75 mM) in the same bioassays.
Visnagin showed the most promising activity. It had significant contact post-emergence herbicidal activity on velvetleaf (Abutilon theophrasti) and crabgrass (Digitaria sanguinalis) during greenhouse tests at 2 kg ai ha-1. Moreover, its effect at 4 kg ai ha-1 against velvetleaf, crabgrass and barnyardgrass (Echinochloa crus-galli) was comparable to the bioherbicide pelargonic acid at the same rate. These results support visnagin’s potential as bioherbicide or lead for the development of a new herbicide.
Additionally, our results suggest that the mode of action of these furanochromones is a process involving multiple targets: membranes destabilization, photosynthetic efficiency reduction, and cell division inhibition. The herbicidal activity could be related to the potential phototoxicity associated with this type of compound. However, although the membrane destabilization was intensified after an irradiation period, the phytotoxic activity of these natural compounds was not light-dependent.
In conclusion, the plant extract screening method developed in this work enabled the identification of two natural compounds whose herbicidal activity is hereby reported for the first time.


Screening of an aqueous plant extract library for antibiotic activities against PhoP/PhoQ two-component system in Salmonella enterica.

M. G. Mediavilla, G. Viarengo, M. L. Travaini, G. Sosa, E. Caccarelli& E. García-Véscovi. XI CongresoArgentino de Microbiología General (SAMIGE) (2015) Córdoba, Argentina.

The Salmonella enterica serovar Typhimurium (S. Typhimurium) PhoP/PhoQ system is an orthodox two-component system that serves as a master regulator of this bacterium virulence. The regulon governed by this system is globally regulated by Mg2+ limitation and subsets of genes respond to different signals such as mild acidic pH, cationic antimicrobial peptides or unsaturated fatty acids. Taking into consideration the relevant role of PhoP/PhoQ system in the adaptation to environmental challenges during interaction of the bacterium with the host and that it can only be found in prokaryotes, low eukaryotes and plants, the system becomes an ideal target to search for new compounds in order to prevent/control S. Typhimurium virulence in mammalian hosts. Plant extracts are sources of compounds with exceptional chemical diversity that constantly gives rise to novel therapeutic agents. In this work, we carried out a screening of aqueous extracts of native plant species from Provincia de Chaco, Argentina, collected during a dry season to identify naturally occurring molecules that would modulate PhoP/PhoQ activity. To accomplish this task, we performed b-galactosidase activity assays in a 96-multiwell plate system to quantitatively asses the action of the extracts on the expression of PhoP-dependent reporters. We tested the activity of 6 different PhoP activated genes with transcriptional fusions to lacZ when bacteria were grown overnight in LB (activating condition), LB + MgCl2 (repressing condition) and LB + plant extracts (test condition) either in 1 mL final volume in assay tubes or in 200 mL final volume in 96-multiwell plates. Of 38 initial lyophilized extracts we determined sub-inhibitory concentrations (in the 0,01 – 5 mg/mL range) and the regulatory effect on the different reporter strains. We selected 10 of these extracts to continue the characterization: 9 showed a repressing effect towards the reporter genes under study while only one (53H) unexpectedly showed repression of most reporters tested but activation of two of them (virK::lacZ and pcgO::lacZ ). There is no previously reported relationship between these particular genes. We are currently pursuing the isolation and identification of the compounds responsible for the repressing/activating effects of the extracts, starting with a bioguided sub-fractionation approach. We are particularly focusing in extract 53H, to also determine whether there is a functional relationship between the activated genes. In sum, we successfully set up a protocol to test a large library of samples in a short time in order to establish a high throughput screening method to test and identify bioactive compounds with modulatory effect on the Salmonella enterica PhoP/PhoQ regulatory system.


Phytotoxicity and antiproliferative activity on tumor cells in vitro of plant extracts.
Travaini, M. L.; García Labari I., Carrillo, N.; Ceccarelli, E. A.; Girardini, J. & Sosa, G. M. L Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB) (2014) Rosario, Argentina.

The interaction of plants with the environment and other organisms causes them to make compounds with diverse biological activities. These compounds are used as active ingredients for many applications. It is estimated that 85% of the world flora is still unexplored. Our goals are to identify plant extracts as source of active ingredients for agro and pharma industry. Therefore we evaluated the phytotoxic activity of plant extracts, as well as, their capacity to inhibit in vitro the proliferation of tumor cell lines. A total of 103 aqueous extracts were prepared from 62 plant species collected in Argentina. Germination assays were performed using all these extracts against two dicot and three monocot species. Four extracts were interesting because they significantly inhibited germination of these five species at 1 and 8 mg/mL. In addition, they showed pre- and post-emergence negative effect on plant growth at 1 mg/mL. On the other hand, four extracts showed anti-proliferative activity against the tumor cell line MDA-MB-231, from breast adenocarcinoma. Moreover, other four extracts were active against the H1299 line, from lung carcinoma. The proliferation inhibition was over than 50% when a dilution 1/2000 of each extract was applied. These results show promising possibilities for these samples and identification of the molecules responsible for the effects is in progress.


Búsqueda de inhibidores de la germinación y/o crecimiento con potencial aplicación como agroquímicos.

María Lucía Travaini; E. A. Ceccarelli; N. J. Carrillo y G. M. Sosa. XI Simposio Argentino y XIV Simposio Latinoamericano de Farmacobotánica. I Congreso Latinoamericano de Plantas Medicinales (2013) Rosario, Argentina.

La pérdida de actividad de algunos herbicidas convencionales y la evolución de resistencia hacia muchos de ellos ha generado la necesidad de encontrar nuevos principios activos con mecanismos de acción diferentes a los conocidos. En este sentido, los productos naturales de las plantas ofrecen una fuente de moléculas diversas. Particularmente, la presencia de ciertos metabolitos fitotóxicos se ha asociado a especies colonizadoras o invasivas y estaría controlada por factores genéticos así como medioambientales. En este contexto, planteamos una búsqueda de inhibidores de la germinación, a partir de extractos vegetales, que puedan ser utilizados en el desarrollo de agroquímicos. Para ello se recolectaron especies que exhibían un comportamiento invasivo, en regiones de Argentina que presentan condiciones climáticas y geográficas adversas. Utilizando los distintos órganos de las mismas se prepararon extractos acuosos y se evaluó su fitotoxicidad contra lechuga (Lactuca sativa). De esta manera se seleccionaron 27 extractos que inhibieron la germinación de dicha especie al 100%. Usando diferentes concentraciones de cada uno de éstos se realizaron nuevos ensayos de germinación de lechuga y especies consideradas modelo de malezas: moha (Setaria itálica), ryegrass anual (Lolium multiflorum) y avena (Avena sativa). Se destacaron particularmente los extractos de hoja 118 y 1429, y el 1503 de fruto. El primero proveniente de una especie recolectada en el Sureste de la provincia de Santiago del Estero; y los dos siguientes, en el Noroeste de Santa Fe. No pueden detallarse las especies puesto que existe un acuerdo de confidencialidad. Estos extractos mostraron el CI50 más bajo para inhibir la germinación de lechuga, en un rango de 1,1-3,2 mg/mL de extracto seco, y generaron porcentajes de inhibición de la germinación de malezas superiores al 80% cuando fueron aplicados a una concentración del 25%. Al realizar curvas de crecimiento de lechuga y ryegrass anual en presencia de los extractos destacados, éstos inhibieron significativamente el crecimiento y desarrollo de ambas especies luego de una semana de tratamiento. Los resultados expuestos hasta aquí han permitido identificar al menos tres extractos vegetales atractivos como potencial fuente de compuestos con actividad herbicida.


Aqueous extracts from plants with phytotoxic activity.

Travaini, M. L.; Carrillo, N. J.; Ceccarelli, E. A.; Sosa G. XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB) (2012) Mendoza, Argentina.

The extensive use of synthetic herbicides directed against a limited number of targets to control weeds has accelerated the rate of appearance of resistance among them. The use of new substances with different sites of action would reduce that problem. In that sense, we propose the use of phytotoxic compounds isolated from plants. Several known vegetal species release germination and/or growth inhibitors as a strategy to colonize or invade grounds occupied by other plants. We collected samples (organs and surrounding soil) of plants that exhibited an invasive behaviour in different regions of Argentina. We also harvested plants popularly known for their medicinal use. A total of 2103 samples were processed. Aqueous extracts were obtained from each sample and their inhibitory activity was tested in assays of lettuce and agronomic seeds germination. We detected that 251 extracts inhibited lettuce germination at 100%. Moreover, 4 extracts were selected because they showed the lowest IC50 (below 3 mg/mL) when tested for lettuce germination inhibition and produced also a post germination effect. Longer exposures of the seeds to these extracts produced an increase on inhibition on lettuce germination and growth. Particularly, the effect on germination was irreversible: after an exposition of seeds to these 4 extracts normal levels of germination were never recovered.


Screening of germination inhibitors from plant extracts.

Travaini, M. L.; Ceccarelli, E. A.; Carrillo, N. J.; Sosa G. XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB) (2011) Potrero de los Funes, Argentina.

Several plant species release germination and/or growth inhibitors as a strategy to colonize and invade grounds occupied by other plants. As a result, these plants populate successfully the bare ground or displace other native plant communities. It is known that the production of these substances increases if plants grow in a harsh environment under stressful conditions. We have collected plant species that exhibited an invasive behavior in regions of Argentina with hostile geography and harsh environments. We have also harvest those plants popularly known for their medicinal use. Using parts and soil of these plants, aqueous extracts were obtained (8 g material/70 mL water). These extracts were tested for their inhibition activity in germination assays of lettuce. Extracts that produced inhibition were then tested on the germination of seeds of agronomic interest. 804 extracts were prepared and 184 of them inhibited lettuce germination at 100%: 98 were derived from Chaco and Santiago del Estero plants, 32 from Cordoba and San Luis and 54 from medicinal species. Regarding the distribution of extracts with inhibition activity, most of them were obtained from leaves (52%), followed by stems (14%) and flowers (12%). Among the extracts used in the germination of agriculturally important species, 23 were noted for their selectivity or aggressiveness in general.

EXPERIENCES

Regions where we have collected plants.

CONTACT