In silico screening of antifolate based novel inhibitors from Brucea mollis Wall. ex kurz against quadruple mutant drug resistant PfDHFR.

Plasmodium falciparum is the most lethal form of the genus Plasmodium which causes malaria, a 'disease of antiquity'. Globally it affects the health and socio-economic development of a large population especially in Sub-Saharan Africa and Southeast Asia. The Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) is an important target of antimalarial drugs. Mutations at the active site of PfDHFR have resulted in decrease drug binding affinity of DHFR-inhibitors. In the present study we selected ten compounds of Brucea mollis Wall. Ex kurz and checked for their drug likeness using various computational tools and potential interactions with PfDHFR by molecular docking study. Soulameanone, a quassinoid of Brucea mollis Wall. Ex kurz showed better binding affinity when compared to pyrimethamine for both wild and quadruple mutant drug resistant PfDHFR. In addition, similar isomers of soulameanone were screened for their drug likeness and to study their interactions with PfDHFR. Twenty three compounds showed better binding affinity compared to soulameanone.

In vitro and in vivo antiplasmodial activity of the root extracts of Brucea mollis Wall. ex Kurz.

Malaria control is compromised worldwide by continuously evolving drug-resistant strains of the parasite demanding exploration of natural resources for developing newer antimalarials. The northeastern region of India is endemic for malaria characterized by high prevalence of drug-resistant Plasmodium falciparum strains. Many plants are used by the indigenous communities living in the northeast India in their traditional system of medicine for the treatment of malarial fever. Folklore claim of antimalarial property of one such plant Brucea mollis was evaluated in vitro and in vivo for antiplasmodial activity. Crude extracts from dried B. mollis root powder were prepared through soxhlet extraction using petroleum ether, methanol, and water sequentially. Methanol extract was further partitioned between chloroform and water. These extracts were tested in vitro against laboratory-adapted chloroquine-sensitive and chloroquine-resistant strains of P. falciparum. In in vitro evaluation, extracts were found more active on the chloroquine-sensitive strain. Methanolic-chloroform (IC(50) 5.1 µg ml(-1)) and methanolic-aqueous (IC(50) 13.9 µg ml(-1)) extracts recorded significant in vitro antiplasmodial activity which was also supported by their promising in vivo activity (ED(50) 72 and 30 mg kg(-1) bw day(-1), respectively) against chloroquine-resistant Plasmodium yoelli N-67 strain in Swiss albino mice. Methanolic-aqueous extract-treated mice survived on average for 14 days that was comparable to the reference drug chloroquine. This is the first report of antiplasmodial activity of B. mollis validating the traditional use of this plant as antimalarial in the northeast India and calls for further detailed investigations.

Effect of different organic manures/composts on the herbage and essential oil yield of Cymbopogon winterianus and their influence on the native AM population in a marginal alfisol.

Four organic amendments: leaf compost (LC), vegetable compost (VC), poultry manure (PM) and sewage sludge (SSL) applied at four doses (40, 80, 100 and 120 tha(-1)) were evaluated for their effect on the herbage yield, essential oil content and inoculum potential (IP) of native arbuscular mycorrhizal fungi (AMF) on three varieties of Java citronella, Cymbopogon winterianus Jowitt (Manjusha, Mandakini, and Bio-13). PM applied at 100 t ha(-1) followed by SSL increased the herbage, essential oil content and dry matter yield significantly. Bio-13 performed better and produced the highest herbage, essential oil and dry matter yield. The type and dose of the various organic amendments also significantly influenced the indigenous AMF infectious propagules in soil. Highest number of AMF propagules were recorded in the LC amended plots in all the three varieties. Amongst the varieties, highest native mycorrhizal inoculum was recorded in the Bio-13. Least number of AM infectious propagules were recorded in the Mandakini plants grown in 40 t ha(-1) SSL.

Malaria control in a forest camp in an oil exploration area of Upper Assam.

BACKGROUND: Assam, in north-east India, is extremely rich in hydrocarbon deposits and the oil industry is the major contributor to its economy. A large number of oil fields and related installations in Assam are located in forest areas or on their fringes where malaria is a serious problem among field staff and security personnel, adversely affecting oil production. We carried out an operational research study for one year in a forest-based industrial security camp of Dibrugarh district and developed an effective malaria control strategy for such areas. METHODS: The specific strategy was formulated and implemented after taking into account the local epidemiology of malaria, vector's ecology and malaria risk behaviour of the camp inmates. The strategy was based on reducing the man-vector contact, using deltamethrin-treated mosquito nets in conjunction with mosquito repellent cream and weekly chemoprophylaxis with 300 mg chloroquine. The impact of the strategy was monitored entomologically and epidemiologically for one year after implementation. RESULTS: The mean landing rate of Anopheles dirus, the vector mosquito in the camp area, was 5.03 per person per night during the monitoring. In spite of such a high density of the vector, the man-vector contact was effectively checked by the intervention measures adopted. As a result, the incidence of malaria in the camp was reduced by > 90% as compared to previous years and the number of malaria cases came down from 6.7 per 1000 man-nights in 1998-99 to 0.06 in 2000-01. Mortality due to malaria was completely eliminated. CONCLUSION: Control of malaria should be based on the local determinants of transmission. The use of insecticide-treated mosquito nets in conjunction with a mosquito repellent cream is a good intervention for controlling Anopheles dirus-transmitted malaria in the forests of north-east India. The control module developed on the principle of reducing man-mosquito contact is easy to implement, cost-effective and replicable in similar forest-based locations.