Biological activities of nitidine, a potential anti-malarial lead compound

International audienceAbstract Background Nitidine is thought to be the main active ingredient in several traditional anti-malarial remedies used in different parts of the world. The widespread use of these therapies stresses the importance of studying this molecule in the context of malaria control. However, little is known about its potential as an anti-plasmodial drug, as well as its mechanism of action. Methods In this study, the anti-malarial potential of nitidine was evaluated in vitro on CQ-sensitive and -resistant strains. The nitidine's selectivity index compared with cancerous and non-cancerous cell lines was then determined. In vivo assays were then performed, using the four-day Peter's test methodology. To gain information about nitidine's possible mode of action, its moment of action on the parasite cell cycle was studied, and its localization inside the parasite was determined using confocal microscopy. The in vitro abilities of nitidine to bind haem and to inhibit β-haematin formation were also demonstrated. Results Nitidine showed similar in vitro activity in CQ-sensitive and resistant strains, and also a satisfying selectivity index (> 10) when compared with a non-cancerous cells line. Its in vivo activity was moderate; however, no sign of acute toxicity was observed during treatment. Nitidine's moment of action on the parasite cycle showed that it could not interfere with DNA replication; this was consistent with the observation that nitidine did not localize in the nucleus, but rather in the cytoplasm of the parasite. Nitidine was able to form a 1-1 complex with haem in vitro and also inhibited β-haematin formation with the same potency as chloroquine. Conclusion Nitidine can be considered a potential anti-malarial lead compound. Its ability to complex haem and inhibit β-haematin formation suggests a mechanism of action similar to that of chloroquine. The anti-malarial activity of nitidine could therefore be improved by structural modification of this molecule to increase its penetration of the digestive vacuole in the parasite, where haemoglobin metabolization takes place

Analyzing potential age cohort effects in car ownership and residential location in the metropolitan region of Amsterdam

Previous research on car ownership has described ownership using a combination of socio-economic factors, demographics, individual preferences and residential factors. However, over the years people's attitudes towards car ownership have changed as new generations are being formed. A new generation of young adults has a different view on car ownership compared to the older generation when car ownership was still a display of status. In this research a first attempt is made to disentangle the effects of age on car ownership and residential location. A discrete choice modelling approach is used where we jointly model car ownership and residential location in the metropolitan region of Amsterdam. We will start from the multinomial logit model and from there try more complex models which capture correlation among alternatives, and introduce a cohort effect for people of a certain age using a nested panel model. The main result of the model shows that car ownership in the city shows more variation in age than car ownership outside of the city

Understanding the relation between travel duration and station choice behavior of cyclists in the metropolitan region of Amsterdam

With 35,000 km of bicycle pathways, cycling is common among persons of all ages less than 65 years in the Netherlands. Bicycle is often seen as a standalone travel mode but when integrated as part of a multimodal trip with train, it can be an important solution for long distance journeys, offering increased flexibility and faster access time compared to other travel modes. In this paper we investigate which factors influence departure station choice on combined bicycle–train and bicycle-metro trips in the metropolitan region of Amsterdam. Data from a mobile app was used to track an individual’s travel behavior over the years 2018 and 2019. A discrete choice model was estimated to see whether people prefer to park their bicycle at the station with the shortest travel duration or one of the stations with a longer travel duration. The final results show that level of education and age negatively influence the choice for cycling to the second closest station. Furthermore, the results show that people with an origin inside Amsterdam prefer to travel to a train station regardless of their destination

Bicycle parking in station areas in the Netherlands

Cities in the Netherlands have encouraged cycling in order to create a more healthy, liveable and sustainable environment. Accordingly, cycling has become an important travel mode in cities for both unimodal and multimodal travel. Consequently, the increase of bicycle use results in an increase in the demand for bicycle parking, thus encouraging illegal bicycle in station areas where supply is unable to meet demand. As space becomes scarce in these areas, managing the existing parking supply becomes crucial in the urban environment. This research attempts to explain bicycle parking behavior by finding determinants for parking near a station with a metro service, train service or both services at the same location. The results not only show that the determinants for parking in these station areas differ, but also that each station areas attracts different groups of people

Analysis of additivity and synergism in the anti-plasmodial effect of purified compounds from plant extracts

In the search for antimalarials from ethnobotanical origin, plant extracts are chemically fractionated and biological tests guide the isolation of pure active compounds. To establish the responsibility of isolated active compound(s) to the whole antiplasmodial activity of a crude extract, the literature in this field was scanned and results were analysed quantitatively to find the contribution of the pure compound to the activity of the whole extract. It was found that, generally, the activity of isolated molecules could not account on their own for the activity of the crude extract. It is suggested that future research should take into account the “drugs beside the drug”, looking for those products (otherwise discarded along the fractionation process) able to boost the activity of isolated active compounds

La simalikalactone E, molécule antipaludique et anticancer = Simalikalactone E, anti-malarial and anticancer molecule

En octobre dernier, le Prix 2013 de l’innovation pour le Sud décerné par l’Institut de recherche pour le développement (IRD) récompensait la découverte d’une molécule aux propriétés miraculeuses : la simalikalactone E. Isolé de Quassia amara, une plante médicinale amazonienne, cette molécule est à la fois un antipaludique et un anticancer. Cette découverte permettra-t-elle à la plante d’accéder au statut des grandes plantes médicaments qui ont bouleversé la thérapeutique en sauvant des milliers de vies ? C’est l’espoir nourri par les chercheurs. Histoire d’une découverte

Quassia “biopiracy” case and the Nagoya Protocol: A researcher's perspective

International audienceBiopiracy accusations are common in the world of biodiversity research. At the end of 2015, a French NGO accused researchers from the Institut de Recherche pour le Développement (IRD) of biopiracy. These researchers had applied for a patent for a natural bioactive molecule against malaria and cancer, the Simalikalactone E, isolated from Quassia amara L. (Simaroubaceae) leaves. This biopiracy allegation triggered a huge wave of attacks from the media and social networks, and vehement recrimination from political officials in French Guiana against researchers who have been accused of ethical misconduct, by stealing the traditional knowledge of indigenous people. These accusations were made in the contentious context of the ratification of the Nagoya Protocol in the frame of implementing the French law on biodiversity, nature and landscapes. So, in an atmosphere of heightened emotions it is crucial to understand the issues behind these accusations. We describe herein the genesis of our discovery, present the detractors' arguments, and discuss the consequences of such biopiracy denunciations for scientific research. We also address our concerns about the gap between rhetoric and reality and the real impact of the Nagoya Protocol on biodiversity conservation

Quassia "biopiracy" case and the Nagoya Protocol : a researcher's perpective

Biopiracy accusations are common in the world of biodiversity research. At the end of 2015, a French NGO accused researchers from the Institut de Recherche pour le Développement (IRD) of biopiracy. These researchers had applied for a patent for a natural bioactive molecule against malaria and cancer, the Simalikalactone E, isolated from Quassia amara L. (Simaroubaceae) leaves. This biopiracy allegation triggered a huge wave of attacks from the media and social networks, and vehement recrimination from political officials in French Guiana against researchers who have been accused of ethical misconduct, by stealing the traditional knowledge of indigenous people. These accusations were made in the contentious context of the ratification of the Nagoya Protocol in the frame of implementing the French law on biodiversity, nature and landscapes. So, in an atmosphere of heightened emotions it is crucial to understand the issues behind these accusations. We describe herein the genesis of our discovery, present the detractors' arguments, and discuss the consequences of such biopiracy denunciations for scientific research. We also address our concerns about the gap between rhetoric and reality and the real impact of the Nagoya Protocol on biodiversity conservation