An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.     

Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist

Montelukast and Zafirlukast are known leukotriene receptor antagonists prescribed in asthma treatment. However, these fall short as mono therapy and are frequently used in combination with inhaled glucocorticosteroids with or without long acting beta 2 agonists. Therefore, it is of interest to apply ligand and structure based virtual screening strategies to identify compounds akin to lead compounds Montelukast and Zafirlukast. Hence, compounds with structures having 95% similarity to these compounds were retrieved from NCBI׳s PubChem database. Compounds similar to lead were grouped and docked at the antagonist binding site of cysteinyl leukotriene receptor 1. This exercise identified compounds UNII 70RV86E50Q (Pub Cid 71587778) and Sure CN 9587085 (Pub Cid 19793614) with higher predicted binding compared to Montelukast and Zafirlukast. It is shown that the compound Sure CN 9587085 showed appreciable ligand receptor interaction compared to UNII 70RV86E50Q. Thus, the compound Sure CN 9587085 is selected as a potent antagonist to cysteinyl leukotriene receptor 1 for further consideration in vitro and in vivo validation.     

Synthesis and biological evaluation of polyhydroxycurcuminoids

A series of curcumin analogs (1-3, 5a-5t) was synthesized through the condensation of appropriately protected hydroxybenzaldehydes with acetylacetone, followed by deprotection. The antioxidant activity of these analogs was determined by superoxide free radical nitroblue tetrazolium and DPPH free radical scavenging methods and the polyhydroxycurcuminoids (5l-5s) displayed excellent antioxidant activity. These analogs showed cytotoxicity to lymphocytes and promising tumor-reducing activity on Dalton's lymphoma ascites tumor cells.     

Flavonoids, triterpenoids and a lignan from Vitex altissima

A new tetrahydrofuranoid lignan, altissinone (1) and a new acylated flavone C-glucoside, 2'-O-p-hydroxybenzoylorientin (2), were isolated in addition to several known triterpene acids and flavonoids from the ethyl acetate extractives of the leaves of Vitex altissima. The structures of the compounds were established based on interpretation of high resolution NMR (HMQC, HMBC and NOESY) spectral data. The ethyl acetate extract exhibited significant anti-inflammatory activity in rat paw edema model. The flavonoids and triterpene acids showed moderate antioxidant and 5-lipoxygenase enzyme inhibitory activities, respectively.     

Standardisation of Gymnema sylvestre R.Br. by high-performance thin-layer chromatography: an improved method

An improved high-performance thin-layer chromatographic (HPTLC) method for the standardisation of Gymnema sylvestre is reported. The method involves the initial hydrolysis of gymnemic acids, the active ingredients, to a common aglycone followed by the quantitative estimation of gymnemagenin. The present method rectifies an error found in an HPTLC method reported recently.     

Synthesis, stereochemical assignments, and biological activities of homoisoflavonoids

A series of four naturally occurring homoisoflavonoids and eight analogs have been synthesized starting from an appropriately substituted phenol through chroman-4-one, in four steps. The products were assigned as E-isomers based on NMR spectroscopic data. The E-isomers were converted into Z-isomers by photoisomerization. The E- and Z-isomers showed distinct chemical shifts and the differences between (E) and (Z)-homoisoflavonoids in the proton NMR spectra afford a useful method for ascertaining the stereochemistry. The antioxidant activity of homoisoflavonoids was determined by superoxide (NBT) and DPPH free radical scavenging methods. The analog 7-hydroxy-3-[(3,4,5-trihydroxyphenyl)methylene]chroman-4-one displayed excellent activity followed by sappanone A in both the methods and were several times potent than the commercial antioxidants like BHA, BHT, etc. These compounds were evaluated in vitro for their inhibitory activities against 5-lipoxygenase (5-LOX) enzyme. The analog 7-hydroxy-3-[(N,N-dimethylaminophenyl)methylene]chroman-4-one was found to possess potent inhibitory activity and was comparable to that of the standard, nordihydroguiaretic acid. These results suggest that these homoisoflavonoids, with their potent antioxidant and 5-LOX inhibitory activities, may have useful applications as antioxidants and lead compounds for asthma and inflammatory diseases.     

Synthesis of microfolicoumarin, a constituent of Cedrelopsis microfoliata

Microfolicoumarin (1), a prenylcoumarin from Cedrelopsis microfoliata, was synthesized from 2,4,5-trimethoxybenzaldehyde in five steps. 1 did not show significant antioxidative activity, but the key intermediates, esculetin (3) and 5-prenylesculetin (6), exhibited strong antioxidative activity in both the superoxide-radical and 1,1-diphenyl-2-picrylhydrazyl radical-scavenging models.     

Human genome screen to identify the genetic basis of the anti-inflammatory effects of Boswellia in microvascular endothelial cells

Inflammatory disorders represent a substantial health problem. Medicinal plants belonging to the Burseraceae family, including Boswellia, are especially known for their anti-inflammatory properties. The gum resin of Boswellia serrata contains boswellic acids, which inhibit leukotriene biosynthesis. A series of chronic inflammatory diseases are perpetuated by leukotrienes. Although Boswellia extract has proven to be anti-inflammatory in clinical trials, the underlying mechanisms remain to be characterized. TNF alpha represents one of the most widely recognized mediators of inflammation. One mechanism by which TNFalpha causes inflammation is by potently inducing the expression of adhesion molecules such as VCAM-1. We sought to test the genetic basis of the antiinflammatory effects of BE (standardized Boswellia extract, 5-Loxin) in a system of TNF alpha-induced gene expression in human microvascular endothelial cells. We conducted the first whole genome screen for TNF alpha- inducible genes in human microvascular cells (HMEC). Acutely, TNF alpha induced 522 genes and downregulated 141 genes in nine out of nine pairwise comparisons. Of the 522 genes induced by TNF alpha in HMEC, 113 genes were clearly sensitive to BE treatment. Such genes directly related to inflammation, cell adhesion, and proteolysis. The robust BE-sensitive candidate genes were then subjected to further processing for the identification of BE-sensitive signaling pathways. The use of resources such as GenMAPP, KEGG, and gene ontology led to the recognition of the primary BE-sensitive TNF alpha-inducible pathways. BE prevented the TNF alpha-induced expression of matrix metalloproteinases. BE also prevented the inducible expression of mediators of apoptosis. Most strikingly, however, TNF alpha-inducible expression of VCAM-1 and ICAM-1 were observed to be sensitive to BE. Realtime PCR studies showed that while TNF alpha potently induced VCAM-1 gene expression, BE completely prevented it. This result confirmed our microarray findings and built a compelling case for the anti-inflammatory property of BE. In an in vivo model of carrageenan-induced rat paw inflammation, we observed a significant antiinflammatory property of BE consistent with our in vitro findings. These findings warrant further research aimed at identifying the signaling mechanisms by which BE exerts its anti-inflammatory effects.     

Triterpenoid glycosides from Bacopa monnieri

Two triterpenoid glycosides have been isolated along with 10 known saponins from Bacopa monnieri. Structures of the compounds have been elucidated as 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] jujubogenin (1) and 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] pseudojujubogenin (2) by high resolution NMR spectral data and chemical correlations. Further, the chemical compositions of bacosides A and B have been delineated.     

Synthesis and biological activity of isoamoenylin,a metabolite of Dendrobium amoenum

Isoamoenylin (6), a dihydrostilbene from Dendrobium amoenum, was synthesised from 3,4,5-trimethoxybenzaldehyde (1) in four steps with an overall yield of 60%. The spectral data for synthetic 6 are in good agreement with those of the natural product. Isoamoenylin showed moderate antioxidative and weak antibacterial activities.