We describe the results of serology for parasitic infection of 250 foreign workers who were seen at the University of Malaya Medical Centre, UMMC during 7-months period. The 250 foreign workers participated included 114 from Indonesia, 142 from Bangladesh, two from Myanmar and two from Pakistan. Blood samples were taken from these workers and eight tests (amoebiasis, echinococcosis, filariasis, leishmaniasis, malaria, schistosomiasis, toxoplasmosis, and trypanosomiasis) were performed on serum. Among the 250 sera tested, 92 (36.8%) were found to be positive for at least one parasitic infection. There was one case where the serum was found positive for 5 tests. The most common antibody detected in those positive sera was antibody for toxoplasma (80.%), followed by filaria (32.8%) and amoeba (30%). Other tests showed low percentage of infection with schistosomiasias, 10%; echinococcosis, 6% and malaria, 3.6%. None of the foreign workers were found positive for leishmaniasis or trypanosomiasias.
Leishmaniasis is a vector-borne disease caused by the protozoan parasite Leishmania found in tropical and sub-tropical areas, affecting 12 million people around the world. Only few treatments are available against this disease and all of them present issues of toxicity and/or resistance. In this context, the development of new antileishmanial drugs specifically directed against a therapeutic target appears to be a promising strategy. The GDP-Mannose Pyrophosphorylase (GDP-MP) has been previously shown to be an attractive therapeutic target in Leishmania. In this study, a chemical library of 5000 compounds was screened on both L. infantum (LiGDP-MP) and human (hGDP-MP) GDP-MPs. From this screening, oncostemonol D was found to be active on both GDP-MPs at the micromolar level. Ten alkyl-resorcinol derivatives, of which oncostemonols E and J (2 and 3) were described for the first time from nature, were then evaluated on both enzymes as well as on L. infantum axenic and intramacrophage amastigotes. From this evaluation, compounds 1 and 3 inhibited both GDP-MPs at the micromolar level, and compound 9 displayed a three-times lower IC50 on LiGDP-MP, at 11 µM, than on hGDP-MP. As they displayed mild activities on the parasite, these compounds need to be further pharmacomodulated in order to improve their affinity and specificity to the target as well as their antileishmanial activity.
The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.
Phytochemical investigation of Beilschmiedia alloiophylla has resulted in the isolation of one new alkaloid, 2-hydroxy-9-methoxyaporphine (1), and ten known natural products, laurotetanine (2), liriodenine (3), boldine (4), secoboldine (5), isoboldine (6), asimilobine (7), oreobeiline (8), 6-epioreobeiline (9), β-amyrone (10), and (S)-3-methoxynordomesticine (11). Chemical studies on the bark of B. kunstleri afforded compounds 2 and 4 along with one bisbenzylisoquinoline alkaloid, N-dimethylphyllocryptine (12). Structures of compounds 1-12 were elucidated on the basis of spectroscopic methods. All of these isolates were evaluated for their anti-acetylcholinesterase (AChE), anti-α-glucosidase, anti-leishmanial and anti-fungal activities. Compounds 1-12 exhibited strong to moderate bioactivities in aforementioned bioassays.
We report a case of visceral leishmaniasis (kala azar) in a 28 year old Bangladeshi migrant. The patient had migrated to Malaysia 9 months prior to admission to our hospital. He was employed in a glove factory. His illness began one week prior to presentation with high swinging fever, chest pain and substantial weight loss. On examination, he was found to be cachetic, with cervical and inguinal lymphadenopathy and niassive hepatosplenomegaly. Investigations revealed a pancytopaenia with a Hb of 9.9 g/L, WBC 3.10 x 10^9/L and a platelet count of 29 x 10g/L. Liver function test revealed an elevated alkaline phosphatase 380 I.U./L and transanlinases AST 169 I.U/L and ALT 95 I.U./L. The serum albumin was 19 g/L. Blood for malaria parasite was negative. A bone marrow examination was performed to look for LD bodies and to exclude haematological malignancies. The bone marrow examination revealed multiple LD bodies. Serology for leishmania was strongly positive. The patient was heated with atnphotericin B to a total dose of 0.6 g. There was resolution of his fever and reduction in the size of the liver and spleen at the end of therapy. There was also a steady gain in his weight. The patient unfortunately failed to return for subsequent follow-ups