Legados de la audacia: Caldas, Humboldt y el conocimiento sobre las quinas, 1801-1821 / Legacies of boldness: Caldas, Humboldt and knowledge about cinchonas, 1801-1821

Resumen El artículo reflexiona sobre la circulación de conocimiento en torno a las plantas de quina. Francisco José de Caldas y Alexander von Humboldt se interesaron por su taxonomía, distribución, comercio, explotación, producción y conservación. Las observaciones del primero fueron mejores, pero sus aportes fueron silenciados por el segundo y por otros actores como José Celestino Mutis. Caldas cambió desde una posición pasiva y de aceptada subalternidad, hasta una de reclamo, pero sus argumentos no tuvieron mayor difusión, en parte porque sus resultados no favorecían intereses comerciales y carecía de redes. Caldas usó dispositivos similares a los de Humboldt para apropiar y sistematizar conocimientos sobre las quinas, silenciando a varias fuentes.

Abstract This article examines the circulation of knowledge about Cinchona plants. Francisco José de Caldas and Alexander von Humboldt were interested in their taxonomy, distribution, trade, exploitation, production and conservation. The former's observations were better, but his contributions were silenced by Humboldt and other actors such as José Celestino Mutis. Caldas changed from a passive position of accepted subordination to one of self-advocacy, but his arguments were not widely publicized, in part because his results did not favor commercial interests and he lacked connections. Caldas used similar techniques to Humboldt to appropriate and systematize knowledge about cinchonas, silencing various sources.

Cinchona L. "Árbol de la Quina": repoblamiento y reforestación en el Perú / Cinchona L. "Quina Tree": Repopulation and reforestation in Peru

Resumen Este trabajo se centra en las recientes decisiones tomadas por el Ministerio de Agricultura del Perú sobre la recolección, propagación y siembra de especies de quina. Señalamos las deficiencias de estas decisiones a la luz de los avances en el conocimiento de la taxonomía y sistemática de Cinchona. Destacamos el papel de la ciencia analizando e informando sobre las decisiones en el uso sostenible de los recursos naturales.

Abstract This work focuses about the recent decisions made by the Ministry of Agriculture of Peru on the collection, propagation, and sowing of Cinchona species are reasons to point out the deficiencies of these decisions in light of advances in the knowledge of Cinchona taxonomy and systematics. We emphasize the role of the science analysing and informing about decisions in the sustainable use of natural resources.

Asymmetric Morita-Baylis-Hillman Reaction of Conjugated Nitroalkene with Activated Aldehyde Catalyzed by Cinchona Alkaloids / 中国药师

Objective:To develop a catalytic system for the asymmetric Morita-Baylis-Hillman ( MBH) reaction of conjugated ni-troalkene with activated aldehyde, and screen out the chiral catalysts with high activity and enantioselectivity. Methods: Totally 21 chiral organocatalysts were applied in the asymmetric MBH reaction ofβ-nitrostyrene with ethyl glyoxylate, and the ee value was deter-mined by chiral HPLC. The effects of temperature, solvent and substrate ratio on the catalytic reaction were investigated. Results: In the presence of cinchona alkaloid catalyst (DHQ)2AQN, β-nitrostyrene reacted with ethyl glyoxylate in toluene at 0℃ affording the MBH adduct in 60% yield with good enantioselectivity (up to 56.9% ee). Conclusion: The bis-cinchona alkaloids with aromatic bridging group are the efficient catalysts for the asymmetric MBH reaction ofβ-nitrostyrene with ethyl glyoxylate, and moderate isolated yield and enantioselectivity are obtained.

Historical story on natural medicinal chemistry: Isolation, structure, and total synthesis of quinine / 中草药

Quinine is a very famous natural medicine that has saved millions of lives, even being believed to affect the development process of human beings. The study of quinine has left a very important record in the history of science. In this paper, the historical stories on the discovery and study of quinine are summarized in memory of the great discoveries and in honor of the scientists. It also aims at providing the references for future related research. This article is one of the series of historical stories on natural product chemistry written by the authors.

Cuantificación de quinina en extractos de Cinchona pubescens y evaluación de la actividad antiplasmodial y citotóxica / Quantification of quinine in extracts from stems Cinchona pubescens and evaluation of antiplasmodial and cytotoxic activity

Plants belonging to the genus Cinchona L. (Rubiaceae), whose active ingredient is quinine, was used for centuries to treat malaria. Plants of this genus are a potential source of new structural templates in the search for new antimalarial candidates. This study aimed to the identification, quantification of quinine and other metabolites present in extracts of different polarity of the stems of Cinchona pubescens Vahl. , oxoquinovic acid isolation, antiplasmodial activity, and measuring its cytotoxic effect. The results show a high activity to antiplasmodial alkaloids extract (IC50 = 2.20 +/- 0.0325 ug/mL), cytotoxicity (CC50 = 80.2 +/- 12.2 ug/mL), and a quinine content of 21.3+/-0.0247 ppm. The compound known as acid antiplasmodial activity oxoquinovic presented in IC50 = 11.3 +/- 0.741 ug/mL, and cytotoxicity CC50 = 72.4 +/- 3.85 ug/mL. These results motivate phytochemical studies in the search for active structural analogues quinine and quinolinic core as a source of new antimalarial agents.

Las plantas pertenecientes al género Cinchona L. (familia Rubiaceae), cuyo principio activo es la quinina, fueron utilizadas durante siglos para tratar la malaria. Este género es una fuente potencial de nuevas plantillas estructurales en la búsqueda de nuevos candidatos antimaláricos. El presente trabajo tuvo como objetivo la identificación y, cuantificación de la quinina y de otros metabolitos presentes en los extractos de diferente polaridad, de los tallos de Cinchona pubescens Vahl. , el aislamiento del ácido oxoquinóvico, la actividad antiplasmodial y, además, la medición de su efecto citotóxico. Los resultados muestran una alta actividad antiplasmodial para el extracto de los alcaloides (IC50 = 2,20 +/- 0,0325 ug/mL), una baja citotoxicidad (CC50 = 80,2 +/- 12,2 ug/mL), y un alto contenido de quinina el cual fue 21,3+/-0,0247 ppm. El compuesto ácido oxoquinóvico presentó una actividad antiplasmodial de IC50 = 11,3 +/- 0.741 ug/mL, y una citotoxicidad de CC50 = 72,4 +/- 3,85 ug/mL. Estos resultados motivan los estudios fitoquímicos en la búsqueda de principios activos y análogos estructurales en diferentes especies de Cinchonas como una fuente de nuevos agentes antimaláricos.

Anti-diabetic Activity of Aqueous Extracts of Vitex doniana Leaves and Cinchona calisaya Bark in Alloxan–Induced Diabetic Rats.

Vitex doniana Sweet and Cinchona calisaya WEED are tropical medicinal plants endued with important pharmacological properties. The effects of aqueous extracts of V. doniana leaves and C. calisaya bark on alloxan-induced diabetes mellitus in Wistar albino rats were evaluated. Diabetes mellitus was induced by a single intraperitoneal ( i.p) injection of 150 mg/kg body wt of alloxan monohydrate. The aqueous extracts of V. doniana leaves and C. calisaya bark were administered intraperitoneally to four diabetic groups at same doses of 50 and 100 mg/kg body wt. The actions of the extracts were compared with that of the standard oral hypoglycaemic agent, glibenclamide. Both extracts caused significant (p < 0.001) decreases in blood sugar levels of the rats at both doses tested. At 50 mg/kg body wt. V. doniana leaf extract produced 82.9% reduction in blood sugar level (i.e from 492.8 to 84.5 mg/dl) after four days whereas, C. calisaya caused 64.4% decrease. Unlike C. calisaya bark, V. doniana at both doses tested, was more potent than the reference drug, glibenclamide (0.3 mg/ kg body wt.). The antidiabetic activity of V. doniana did not vary with the dose, whereas the observed effect of C. calisaya decreased with increase in dose. C. calisaya exhibited higher antidiabetic activity at a lower dose of 50 mg/kg body wt. Both medicinal plants therefore possess valuable antidiabetic property. Their effects on the antioxidant status were also investigated. V. doniana and C. calisaya extracts caused increases in the activity of SOD and lipid peroxidation when compared with control, but the increases were lower than that produced by alloxan, indicating attenuation of free radical generation. Quantitative phytochemical analyses of both extracts showed the presence of saponins(0.92%), flavonoids(7.05%), alkaloids(1.8%), and cardiac glycosides(2.8%) in V. doniana, whereas saponins(2.0%), flavonoids(5.0%), alkaloids(6.0%), and cardiac glycosides(3.54%) were detected in C. calisaya.

Avaliação de parâmetros de extração da Cinchona Vahl por métodos farmacopéicos e não farmacopéicos / Extraction parameters from Cinchona pubescens Vahl using pharmacopeia and no pharmacopeia methods

O presente estudo teve como objetivo a otimização de parâmetros cinéticos de extração da Cinchona pubescens Vahl por ultra-som, usando métodos farmacopéicos e não farmacopéicos. Na extração por ultrasom variaram-se o tempo, a massa, a faixa granulométrica, o volume de solvente e o tipo de solvente. Na decocção, as extrações foram feitas no tempo e temperatura descrita na Farmacopéia Brasileira IV, variando-se o sistema solvente. Na extração por maceração variaram-se o tempo e o sistema solvente. O teor de alcalóides quinolínicos foi monitorado por espectrofotometria no UV a 325 nm. O método decocção foi o que apresentou o maior rendimento na extração dos alcalóides, dados equivalentes foram conseguidos com o método ultra-som, no tempo de 5 min e solvente acidificado pH 4, com um rendimento maior ao da maceração. Pela aplicação do planejamento fatorial para o método do ultra-som foi visto que há uma interação entre as variáveis, necessitando de um melhor ajuste entre elas a fim de melhorar a eficiência extrativa do método do ultra-som.

The present study for ultrasound had as objective the optimization of kinetic parameters of extraction of the Cinchona pubescens Vahl, using pharmacopeia and no pharmacopeia methods. In the extraction for ultrasound they had varied the time, the solvent type, the mass, the volume of solvent and grain size of the sample. In the decoction, the extractions had been made according to the time and temperature described in Brazilian Pharmacopeia IV, varying the solvent system. In the extraction for maceration the time and the solvent system had varied. The alkali of the Cinchona pubescens Vahl, was monitored by spectrophotometry in UV 325 nm. The method decoction was the one that presented the biggest income in the alkaloids extraction, given equivalent data had been obtained with the method ultrasound, in the solvent acidified pH 4 and time of 5 min, with a bigger income than the one of the maceration.

Algunos aspectos relacionados con José Celestino Mutis y la medicina / Some Topics in Relation to José Celestino Mutis and Medicine

José Celestino Mutis mostró muy diversos intereses a lo largo de su vida, y se desempeñó en múltiples áreas del conocimiento: matemáticas, mineralogía, astronomía, zoología; sin embargo, la botánica es la más conocida. Mutis fue, ante todo, un médico, con conocimientos profundos y actualizados, formado en la Universidad de Sevilla y en el Colegio Real de Cirugía de Cádiz. Llegó al Nuevo Reino de Granada como médico personal del virrey Pedro Messía de la Cerda, y durante los 47 años que permaneció allí, ejerció siempre su profesión. Se interesó intensamente en el estudio de las quinas, dejando como única obra publicada El Arcano de la quina. Asesoró en materia de salud pública a diferentes virreyes, contribuyendo en variados aspectos, particularmente, en la inoculación como mecanismo preventivo de la viruela. Jugó un papel decisivo en la reapertura de la Facultad de Medicina del Colegio Mayor de Nuestra Señora del Rosario. Algunos de esos logros han hecho que reciba justamente el apelativo de "Padre de la Medicina en Colombia".

José Celestino Mutis showed different interest areas of study and worked in multiple knowledge fields: mathematics, mineralogy, astronomy, zoology and botanic, the one in which is best known. However, he was a medical doctor, whit profound an up to date knowledge. He studied at Sevilla University, and in the Royal College of Cadiz. He arrived to the "Nuevo Reino de Granada" as personal medical doctor of the the viceroy Pedro Messía de la Cerda and during 47 years, period of time he lived there, he always exercised his profession. We showed a special interest in the study of cinchona and the only work he published was El Arcano de la quina. He advised in public health many viceroys and he contributed in different fields but particularly in the prevention of smallpox by inoculation. He played a decisive role in the reopening of the medical school of the Colegio Mayor de Nuestra Señora del Rosario. Some of his achievements justifies the appellative "Father of the Medicine in Colombia".