Malaria continues to be a major public health problem in the Northeastern part of India despite the implementation of vector control measures and changes in drug policies. To develop successful ...vaccines against malaria, it is important to assess the diversity of vaccine candidate antigens in field isolates. This study was done to assess the diversity of Plasmodium falciparum AMA-1 vaccine candidate antigen in a malaria-endemic region of Tripura in Northeast India and compare it with previously reported global isolates with a view to assess the feasibility of developing a universal vaccine based on this antigen.
Patients with fever and malaria-like illness were screened for malaria and P. falciparum positive cases were recruited for the current study. The diversity of PfAMA-1 vaccine candidate antigen was evaluated by nested PCR and RFLP. A selected number of samples were sequenced using the Sanger technique.
Among 56 P. falciparum positive isolates, Pfama-1 was successfully amplified in 75% (n = 42) isolates. Allele frequencies of PfAMA-1 antigen were 16.6% (n = 7) for 3D7 allele and 33.3% (n = 14) in both K1 and HB3 alleles. DNA sequencing revealed 13 haplotypes in the Pfama-1 gene including three unique haplotypes not reported earlier. No unique amino-acid substitutions were found. Global analysis with 2761 sequences revealed 435 haplotypes with a very complex network composition and few clusters. Nucleotide diversity for Tripura (0.02582 ± 0.00160) showed concordance with South-East Asian isolates while recombination parameter (Rm = 8) was lower than previous reports from India. Population genetic structure showed moderate differentiation.
Besides documenting all previously reported allelic forms of the vaccine candidate PfAMA-1 antigen of P. falciparum, new haplotypes not reported earlier, were found in Tripura. Neutrality tests indicate that the Pfama-1 population in Tripura is under balancing selection. This is consistent with global patterns. However, the high haplotype diversity observed in the global Pfama-1 network analysis indicates that designing a universal vaccine based on this antigen may be difficult. This information adds to the existing database of genetic diversity of field isolates of P. falciparum and may be helpful in the development of more effective vaccines against the parasite.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Malaria continues to become a major global health problem, particularly in Sub‐Saharan Africa, Asia, and Latin America. The widespread emergence of resistance to first‐line drugs has further ...bolstered an urgent need for a new and cost‐effective antimalarial(s). Thus, the present study enumerates the synthesis of novel hybrid dimethoxy pyrazole 1,3,5‐triazine derivatives 7(a–j) and their in silico results short‐listed three compounds with good binding energies and dock scores. Docking analysis shows that hydrogen‐bonding predominates and typically involves key residues, such as Asp54, Tyr170, Ile164, and Arg122. The in vitro antimalarial evaluation of three top‐ranked compounds (7e, 7g, and 7h) showed half‐maximal inhibitory concentration values range from 53.85 to 100 μg/ml against chloroquine‐sensitive strain 3D7 of Plasmodium falciparum. Compound 7e may be utilized as a lead for further optimization work in drug discovery due to good antimalarial activity.
Compound 7e show good antimalarial activity against chloroquine‐sensitive strain 3D7 of Plasmodium falciparum.
The present manuscript deals with the development of novel p‐aminobenzoic acid (PABA) associated 1,3,5‐triazine derivatives as antimalarial agents. The molecules were developed via microwave‐assisted ...synthesis and structures of compounds were ascertained via numerous analytical and spectroscopic techniques. The synthesized compounds were also subjected to ADMET analysis. In a docking analysis, the title compounds showed high and diverse binding affinities towards wild (−162.45 to −369.38 kcal/mol) and quadruple mutant (−165.36 to −209.47 kcal/mol) Pf‐DHFR‐TS via interacting with Phe58, Arg59, Ser111, Ile112, Phe116. The in vitro antimalarial activity suggested that compounds 4e, 4b, and 4h showed IC50 ranging from 4.18 to 8.66 μg/ml against the chloroquine‐sensitive (3D7) strain of Plasmodium falciparum. Moreover, compounds 4g, 4b, 4e, and 4c showed IC50 ranging from 8.12 to 12.09 μg/ml against chloroquine‐resistant (Dd2) strain. In conclusion, our study demonstrated the development of hybrid PABA substituted 1,3,5‐triazines as a novel class of Pf‐DHFR inhibitor for antimalarial drug discovery.
Graphical
Microwave‐assisted synthesis of hybrid p‐aminobenzoic acid‐1,3,5‐triazine derivatives and their SAR study as an antimalarial agent.
Gnetum gnemon L. (Gnetaceae) is used traditionally for treating malaria related fever by indigenous people of North East India. In our preliminary study, the ethanol extract of G. gnemon leaves ...showed promising antiplamodial activity against Plasmodium falciparum chloroquine sensitive (3D7) strain in vitro with an IC50 value of 29.4 μg/mL. Therefore, it was further investigated, and by following a bioassay guided approach, 2,3-dihydroxypropyl icosanoate (1), oleic acid (2) and ursolic acid (3) were isolated for the first time from this plant. Compound 3 showed highest antiplasmodial activity with IC50 values of 4.0 and 6.0 μg/mL against chloroquine sensitive (3D7) and resistant (Dd2) strains of P. falciparum, respectively. The antiplasmodial activity of 1 (IC50 9.5 and 11.4 μg/mL) and 2 (IC50 17.6 and 21.1 μg/mL) was moderate. The isolated constituents showed low cytotoxicity against rat skeletal muscle (L6) and human cervical cancer (HeLa) cells. This is the first report on the antimalarial potential of G. gnemon and the isolated compounds may be responsible for its activity. The findings of the study are in line with the ethnopharmacological claim and can be possible leads for future studies.
Anopheles baimaii is a primary vector of human malaria in the forest settings of Southeast Asia including the north-eastern region of India. Here, the genetic population structure and the basic ...population genetic parameters of An. baimaii in north-east India were estimated using DNA sequences of the mitochondrial cytochrome oxidase sub unit II (COII) gene.
Anopheles baimaii were collected from 26 geo-referenced locations across the seven north-east Indian states and the COII gene was sequenced from 176 individuals across these sites. Fifty-seven COII sequences of An. baimaii from six locations in Bangladesh, Myanmar and Thailand from a previous study were added to this dataset. Altogether, 233 sequences were grouped into eight population groups, to facilitate analyses of genetic diversity, population structure and population history.
A star-shaped median joining haplotype network, unimodal mismatch distribution and significantly negative neutrality tests indicated population expansion in An. baimaii with the start of expansion estimated to be ~0.243 million years before present (MYBP) in north-east India. The populations of An. baimaii from north-east India had the highest haplotype and nucleotide diversity with all other populations having a subset of this diversity, likely as the result of range expansion from north-east India. The north-east Indian populations were genetically distinct from those in Bangladesh, Myanmar and Thailand, indicating that mountains, such as the Arakan mountain range between north-east India and Myanmar, are a significant barrier to gene flow. Within north-east India, there was no genetic differentiation among populations with the exception of the Central 2 population in the Barail hills area that was significantly differentiated from other populations.
The high genetic distinctiveness of the Central 2 population in the Barail hills area of the north-east India should be confirmed and its epidemiological significance further investigated. The lack of genetic population structure in the other north-east Indian populations likely reflects large population sizes of An. baimaii that, historically, were able to disperse through continuous forest habitats in the north-east India. Additional markers and analytical approaches are required to determine if recent deforestation is now preventing ongoing gene flow. Until such information is acquired, An. baimaii in north-east India should be treated as a single unit for the implementation of vector control measures.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Biosynthesis of Ag nanoparticles using water extract of Clerodendrum viscosum leaf.•Spherical shaped silver nanoparticles with an average diameter of 28.27 nm.•Exhibited excellent ...antiplasmodial activity against 3D7 strain of P. falciparum.•Demonstrated good anticancer activity against HeLa cells.
Silver nanoparticles (AgNPs) were synthesized using water extract of Clerodendrum viscosum Vent leaf as reducing agent. The synthesized AgNPs were characterized by X-ray diffraction, UV–visible spectroscopy, X-ray photoelectron spectroscopy studies. Spherical shaped AgNPs were confirmed by FE-SEM and HRTEM analysis. NMR and FT-IR spectroscopy analysis suggested participation of biomolecules of C. viscosum extract for bioreduction and capping of AgNPs. These biosynthesize AgNPs exhibited significant antiplasmodial activity against 3D7 sensitive strain of Plasmodium falciparum with IC50 = 2.30 μg/ml. Further, AgNPs were investigated for anticancer property against human cervical cancer (HeLa) cell lines.
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•5 compounds were isolated from Xanthium strumarium L. by bioassay guided method.•Antimalarial efficacy was studied against Plasmodium falciparum 3D7 strain.•Two compounds showed ...excellent antimalarial activity with IC50= 27.25 and 7.14 μM.•Results supported the traditional use of X. strumarium L. for the cure of malaria.
Malaria is a major threat to global health and continues to claim lives of many people each year, especially in developing countries. Xanthium strumarium L., is used by traditional health practitioners in the management of malaria fever in North East India. Bioassay guided fractionation of X. strumarium L. extracts, led to the isolation of five compounds from the aerial part and fruit of Xanthium strumarium, namely, stigmasta-5,22-dien-3β-ol (1), xanthinosin (2), stigmasterol-3-O-β-D-glucopyranoside (3), oleic acid (4) and (E)-2, 3-dihydroxypropyl-octadec-9-enoate (5). Antimalarial potential of isolated compounds were evaluated against 3D7 strain of Plasmodium falciparum by schizont maturation inhibition assay method. The structures of isolated compounds were established by HR-MS, NMR experiments and comparison from literature data. Compounds 2 and 3 showed significant antimalarial properties against 3D7 strain of P.falciparum with IC50 value 27.25 and 7.14μM respectively. The antimalarial activities of xanthinosin (2) and stigmasterol-3-O-β-D-glucopyranoside (3) lend credence to the application of X. strumarium against malaria and thus provides new template for development of antimalarial molecules. X. strumarium has also scope for the development of antimalarial phyto-pharmaceutical with five identified compounds with P.falciparum inhibitory activity as per the drugs and cosmetics act of India (1940, amended 31st December 2016).
This volume comprises eight well-versed contributed chapters devoted to report the latest findings on the intelligent approaches to multimedia data analysis. Multimedia data is a combination of ...different discrete and continuous content forms like text, audio, images, videos, animations and interactional data. At least a single continuous media in the transmitted information generates multimedia information. Due to these different types of varieties, multimedia data present varied degrees of uncertainties and imprecision, which cannot be easy to deal by the conventional computing paradigm. Soft computing technologies are quite efficient to handle the imprecision and uncertainty of the multimedia data and they are flexible enough to process the real-world information. Proper analysis of multimedia data finds wide applications in medical diagnosis, video surveillance, text annotation etc. This volume is intended to be used as a reference by undergraduate and post graduate students of the disciplines of computer science, electronics and telecommunication, information science and electrical engineering. THE SERIES: FRONTIERS IN COMPUTATIONAL INTELLIGENCE The series Frontiers In Computational Intelligence is envisioned to provide comprehensive coverage and understanding of cutting edge research in computational intelligence. It intends to augment the scholarly discourse on all topics relating to the advances in artifi cial life and machine learning in the form of metaheuristics, approximate reasoning, and robotics. Latest research fi ndings are coupled with applications to varied domains of engineering and computer sciences. This field is steadily growing especially with the advent of novel machine learning algorithms being applied to different domains of engineering and technology. The series brings together leading researchers that intend to continue to advance the fi eld and create a broad knowledge about the most recent state of the art.
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