3D7 Strain Research Articles

Development, characterization, and evaluation of withaferin-A and artesunate-loaded pH-responsive acetal-dextran polymeric nanoparticles for the management of malaria

Artemisinin and its derivatives have been commonly used to treat malaria. However, the emergence of resistance against artemisinin derivatives has posed a critical challenge in malaria management. In the present study, we have proposed a combinatorial approach, utilizing pH-responsive acetal-dextran nanoparticles (Ac-Dex NPs) as carriers for the delivery of withaferin-A (WS-3) and artesunate (Art) to improve treatment efficacy of malaria. The optimized WS-3 and Art Ac-Dex NPs demonstrated enhanced pH-responsive release profiles under parasitophorous mimetic conditions (pH 5.5). Computational molecular modeling reveals that Ac-Dex's polymeric backbone strongly interacts with merozoite surface protein-1 (MSP-1), preventing erythrocyte invasion. In-vitro antimalarial activity of drug-loaded Ac-Dex NPs reveals a 1–1.5-fold reduction in IC50 values compared to pure drug against the 3D7 strain of Plasmodium falciparum. Treatment with WS-3 Ac-Dex NPs (100 mg/kg) and Art Ac-Dex NPs (30 mg/kg) to Plasmodium berghei-infected mice resulted in 78.11 % and 100 % inhibition of parasitemia. Notably, the combination therapy comprised of Art and WS-3 Ac-Dex NPs achieved complete inhibition of parasitemia even at a half dose of Art, indicating the synergistic potential of the combinations. However, further investigations are necessary to confirm the safety and effectiveness of WS-3 and Art Ac-Dex NPs for their successful clinical implications.

Molecular Docking, Synthesis and <i>In Vitro</i> Antiplasmodium Assay of Monoketone Curcumin Analogous from 2-Chlorobenzaldehyde

This research aimed to develop new curcumin analogous as antiplasmodium candidates. Six curcumin analogous (1-6) were proposed and docked against three Plasmodium falciparum receptors, namely PfENR, PfLDH, and PfATP6. The docking studies were carried out to predict the interaction among the compounds and receptors as well as their binding affinity. Three curcumin analogous (3, 4, and 6), which displayed specific interactions with the target receptors and possessed the lowest binding affinity were further proceeded to synthesis and in vitro antiplasmodium assay. Synthesis of the analogous 3, 4, and 6 was carried out from 2-chlorobenzadehyde via aldol condensation reaction and the products were obtained in good yields. Their in vitro antiplasmodium activities were then evaluated against P. falciparum FCR3 and 3D7 strains. The results showed that analogous 3, 4, and 6 were active against both strains with low levels of resistance. The in silico evaluation of the physicochemical and pharmacokinetic parameters showed that curcumin analogous displayed a better ADMET profile than curcumin, demonstrating the great potential of the developed curcumin analogous as antiplasmodium candidates.

In vitro antimalarial therapeutic interventions using various combinations of antibiotics and standard antimalarials against multi drug resistant Indian field isolates of Plasmodium falciparum

Resistance to antimalarials is considered to be major cause of increased malaria morbidity and mortality. Present study was undertaken to explore an effective drug combination against selected mutant parasite various combinations using standard antimalarials {Chloroquine diphosphate (CQ), Quinine (QUIN), Mefloquine (MQ), Piperaquine (PPQ), Artemether (ARTM), Arteether (ARTE), Dihydro-artemisinin (DHA), Lumefantrine (LUME)and Atovaquone (ATQ)} belonging to three different classes and two antibiotics, Azithromycin (AZI) and Doxycycline (DOXY) have been tried against K1 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains as well as selected arteether torelant parasite (MZRI-R) and field isolates (MZRI & MZRII) of P. falciparum. SYBR Green I fluorescence (MSF) assay was used to determine IC50 values. Results of present studies highlighted that all the combinations used exhibited additive effect with varying intensity depending upon the drug ratios used. We also observed that combination of ARTM plus LUME was more advantageous than DOXY plus DHA/CQ and AZI plus CQ/ATQ for treatment of multidrug resistant parasites whereas combinations of LUME plus PPQ, ATQ plus DOXY/AZI can be used for treatment of CQ resistant parasite.

Stereochemical insights into enantioselective antiplasmodial lignanamides from the twigs and leaves of Solanum erianthum

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b–2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1–3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.

Repurposing DrugBank compounds as potential Plasmodium falciparum class 1a aminoacyl tRNA synthetase multi-stage pan-inhibitors with a specific focus on mitomycin

Plasmodium falciparum aminoacyl tRNA synthetases (PfaaRSs) are potent antimalarial targets essential for proteome fidelity and overall parasite survival in every stage of the parasite's life cycle. So far, some of these proteins have been singly targeted yielding inhibitor compounds that have been limited by incidences of resistance which can be overcome via pan-inhibition strategies. Hence, herein, for the first time, we report the identification and in vitro antiplasmodial validation of Mitomycin (MMC) as a probable pan-inhibitor of class 1a (arginyl(A)-, cysteinyl(C), isoleucyl(I)-, leucyl(L), methionyl(M), and valyl(V)-) PfaaRSs which hypothetically may underlie its previously reported activity on the ribosomal RNA to inhibit protein translation and biosynthesis. We combined multiple in silico structure-based discovery strategies that first helped identify functional and druggable sites that were preferentially targeted by the compound in each of the plasmodial proteins: Ins1-Ins2 domain in Pf-ARS; anticodon binding domain in Pf-CRS; CP1-editing domain in Pf-IRS and Pf-MRS; C-terminal domain in Pf-LRS; and CP-core region in Pf-VRS. Molecular dynamics studies further revealed that MMC allosterically induced changes in the global structures of each protein. Likewise, prominent structural perturbations were caused by the compound across the functional domains of the proteins. More so, MMC induced systematic alterations in the binding of the catalytic nucleotide and amino acid substrates which culminated in the loss of key interactions with key active site residues and ultimate reduction in the nucleotide-binding affinities across all proteins, as deduced from the binding energy calculations. These altogether confirmed that MMC uniformly disrupted the structure of the target proteins and essential substrates. Further, MMC demonstrated IC50 < 5 μM against the Dd2 and 3D7 strains of parasite making it a good starting point for malarial drug development. We believe that findings from our study will be important in the current search for highly effective multi-stage antimalarial drugs.

Isolation of a facultative methanotroph Methylocystis iwaonis SD4 from rice rhizosphere and establishment of rapid genetic tools for it.

Methanotrophs of the genus Methylocystis are frequently found in rice paddies. Although more than ten facultative methanotrophs have been reported since 2005, none of these strains was isolated from paddy soil. Here, a facultative methane-oxidizing bacterium, Methylocystis iwaonis SD4, was isolated and characterized from rhizosphere samples of rice plants in Nanjing, China. This strain grew well on methane or methanol but was able to grow slowly using acetate or ethanol. Moreover, strain SD4 showed sustained growth at low concentrations of methane (100 and 500ppmv). M. iwaonis SD4 could utilize diverse nitrogen sources, including nitrate, urea, ammonium as well as dinitrogen. Strain SD4 possessed genes encoding both the particulate methane monooxygenase and the soluble methane monooxygenase. Simple and rapid genetic manipulation methods were established for this strain, enabling vector transformation and unmarked genetic manipulation. Fast growth rate and efficient genetic tools make M. iwaonis SD4 an ideal model to study facultative methanotrophs, and the ability to grow on low concentration of methane implies its potential in methane removal.

Unveiling the therapeutic potential of organotellurium(IV) Schiff base complexes through structural elucidation, antimalarial, antioxidant and antimicrobial studies

Infectious diseases have long been a formidable adversary to human health and well-being, presenting a persistent global challenge with far-reaching implication for individuals, communities and societies at large. Thus, with the aim of a combating agent against malarial and oxidant causing ailments, the newly synthesized Organotellurium(IV) complexes with a hydroxynaphthaldehyde Schiff base ligand are proposed in the present research. The structures of the complexes were established through various physical and spectral analysis. The weak electrolytic (8.77 to 35.08 ohm−1 cm2 mol−1) and crystalline nature of the compounds were demonstrated by molar conductivity and TGA, respectively. The ligand and complexes (7a-7f) shows molecular ion peaks at m/z 458.3563, 726.1039, 713.6978, 727.6179, 799.4780, 771.3178 and 799.3978 amu which were well consistent with their formula, revealing formation of compounds. The shifting of ligand's azomethine peak (7.74 ppm) and disappearance of naphthyl hydroxyl proton (12.28 ppm) in 1H NMR spectra confirmed the chelation of ligand with metal ion in proposed manner. In the FT-IR spectra, the complexation of ligand with metal ion was confirmed by disappearance of hydroxyl group (3355 cm−1) band and shifting of C = N (1245 cm−1) and CO (1632 cm−1) band whereas appearance of Te-O (of 285–293 cm−1) and Te-N (458–467 cm−1) bands, revealed the bonding of metal with metal and octahedral nature of the complexes. Optimized structures, HOMO-LUMO energies and associated chemical reactivity descriptors of the compounds were computed by DFT calculations. The in vitro studies demonstrate that the complexes 7c (1.06 ± 0.11 μM) and 7f (1.22 ± 0.05 μM) exhibited moderate inhibition of the Plasmodium falciparum 3D7 strain, complexes 7a (100.96 ± 0.32 μg/mL) and 7d (96.32 ± 0.40 μg/mL) demonstrated the highest free radical quenching ability. Complex 7c displayed the highest antibacterial actions, whereas 7f exhibited the highest antifungal actions against the tested pathogens. Molecular docking and ADMET studies demonstrated enhanced binding affinity of the complexes compared to the Schiff base and their drug-like qualities.

Genetic polymorphism and evidence of signatures of selection in the Plasmodium falciparum circumsporozoite protein gene in Tanzanian regions with different malaria endemicity

BackgroundIn 2021 and 2023, the World Health Organization approved RTS,S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of Plasmodium falciparum circumsporozoite protein (PfCSP), but polymorphisms in the gene raise concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the Pfcsp genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission intensities in Mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country.MethodsThe analysis involved 589 whole genome sequences generated by and as part of the MalariaGEN Community Project. The samples were collected between 2013 and January 2015 from five regions of Mainland Tanzania: Morogoro and Tanga (Muheza) (moderate transmission areas), and Kagera (Muleba), Lindi (Nachingwea), and Kigoma (Ujiji) (high transmission areas). Wright’s inbreeding coefficient (Fws), Wright’s fixation index (FST), principal component analysis, nucleotide diversity, and Tajima’s D were used to assess within-host parasite diversity, population structure and natural selection.ResultsBased on Fws (< 0.95), there was high polyclonality (ranging from 69.23% in Nachingwea to 56.9% in Muheza). No population structure was detected in the Pfcsp gene in the five regions (mean FST = 0.0068). The average nucleotide diversity (π), nucleotide differentiation (K) and haplotype diversity (Hd) in the five regions were 4.19, 0.973 and 0.0035, respectively. The C-terminal region of Pfcsp showed high nucleotide diversity at Th2R and Th3R regions. Positive values for the Tajima’s D were observed in the Th2R and Th3R regions consistent with balancing selection. The Pfcsp C-terminal sequences revealed 50 different haplotypes (H_1 to H_50), with only 2% of sequences matching the 3D7 strain haplotype (H_50). Conversely, with the NF54 strain, the Pfcsp C-terminal sequences revealed 49 different haplotypes (H_1 to H_49), with only 0.4% of the sequences matching the NF54 strain (Hap_49).ConclusionsThe findings demonstrate high diversity of the Pfcsp gene with limited population differentiation. The Pfcsp gene showed positive Tajima’s D values, consistent with balancing selection for variants within Th2R and Th3R regions. The study observed differences between the intended haplotypes incorporated into the design of RTS,S and R21 vaccines and those present in natural parasite populations. Therefore, additional research is warranted, incorporating other regions and more recent data to comprehensively assess trends in genetic diversity within this important gene. Such insights will inform the choice of alleles to be included in the future vaccines.

Identification of domains in Plasmodium falciparum proteins of unknown function using DALI search on AlphaFold predictions

Plasmodium falciparum, the causative agent of malaria, poses a significant global health challenge, yet much of its biology remains elusive. A third of the genes in the P. falciparum genome lack annotations regarding their function, impeding our understanding of the parasite's biology. In this study, we employ structure predictions and the DALI search algorithm to analyse proteins encoded by uncharacterized genes in the reference strain 3D7 of P. falciparum. By comparing AlphaFold predictions to experimentally determined protein structures in the Protein Data Bank, we found similarities to known domains in 353 proteins of unknown function, shedding light on their potential functions. The lowest-scoring 5% of similarities were additionally validated using the size-independent TM-align algorithm, confirming the detected similarities in 88% of the cases. Notably, in over 70 P. falciparum proteins the presence of domains resembling heptatricopeptide repeats, which are typically involvement in RNA binding and processing, was detected. This suggests this family, which is important in transcription in mitochondria and apicoplasts, is much larger in Plasmodium parasites than previously thought. The results of this domain search provide a resource to the malaria research community that is expected to inform and enable experimental studies.

Leaf litter from Cynanchum auriculatum Royle ex Wight leads to root rot outbreaks by Fusarium solani, hindering continuous cropping.

Cynanchum auriculatum Royle ex Wight (CA) is experiencing challenges with continuous cropping obstacle (CCO) due to soil-borne fungal pathogens. The leaf litter from CA is regularly incorporated into the soil after root harvesting, but the impact of this practice on pathogen outbreaks remains uncertain. In this study, a fungal strain D1, identified as Fusarium solani, was isolated and confirmed as a potential factor in CCO. Both leave extract (LE) and root extract (RE) were found to inhibit seed germination and the activities of plant defense-related enzymes. The combinations of extracts and D1 exacerbated these negative effects. Beyond promoting the proliferation of D1 in soil, the extracts also enhanced the hypha weight, spore number, and spore germination rate of D1. Compared to RE, LE exhibited a greater degree of promotion in the activities of pathogenesis-related enzymes in D1. Additionally, caffeic acid and ferulic acid were identified as potential active compounds. LE, particularly in combination with D1, induced a shift in the composition of fungal communities rather than bacterial communities. These findings indicate that the water extract of leaf litter stimulated the growth and proliferation of fungal strain D1, thereby augmenting its pathogenicity toward CA and ultimately contributing to the CCO process.

Design, in silico study, synthesis and evaluation of hybrid pyrazole substituted 1,3,5-triazine derivatives for antimalarial activity

ObjectivesMalaria is a significant global health challenge, particularly in Africa, Asia, and Latin America, necessitating immediate investigation into innovative and efficacious treatments. This work involves the development of pyrazole substituted 1,3,5-triazine derivatives as antimalarial agent. MethodsIn this study, ten compounds 7(a-j) were synthesized by using nucleophilic substitution reaction, screened for in silico study and their antimalarial activity were evaluated against 3D7 (chloroquine-sensitive) strain of P. falciparum. Key findingThe present work involves the development of hybrid trimethoxy pyrazole 1,3,5-triazine derivatives 7 (a–j). Through in silico analysis, four compounds were identified with favorable binding energy and dock scores. The primary focus of the docking investigations was on the examination of hydrogen bonding and the associated interactions with certain amino acid residues, including Arg A122, Ser A108, Ser A111, Ile A164, Asp A54, and Cys A15. The IC50 values of the four compounds were measured in vitro to assess their antimalarial activity against the chloroquine sensitive 3D7 strain of P. falciparum. The IC50 values varied from 25.02 to 54.82 μg/mL. ConclusionAmong the ten derivatives, compound 7J has considerable potential as an antimalarial agent, making it a viable contender for further refinement in the realm of pharmaceutical exploration, with the aim of mitigating the global malaria load.

Synergistic degradation efficiency of nitrogen, phosphorus and microbial dynamic succession driven by a novel strain Gordonia sp. D4 during synthetic wastewater treatment

Nitrogen (N) and phosphorus (P) coexist in the industrial and domestic wastewater posed a pressing challenge for synergistic removal of N and P by bioenhancement. In this study, a novel denitrifying phosphorus-accumulating organism (DPAO) of Gordonia sp. D4, exhibited peak NO3--N, NO2--N, NH4+-N and TP removal efficiencies of 98.11%, 65.02%, 85.34% and 100%, corresponding to 9.30 mg/(L·h), 6.08 mg/(L·h), 3.63 mg/(L·h) and 0.47 mg/(L·h) removal rates, respectively. Strain D4 contained the nitrogen cycling genes narK, narI, narJ, narH, narG, nirB and nirD, as well as the phosphorus cycling genes ppk1, ppk2 and ppx-gppA, which contributes to its excellent simultaneous removal of N and P. More importantly, the addition of D4 into the sequencing batch reactor (SBR) significantly improved the P, TN and NO3--N removal efficiencies by 18.91%, 7.35%, and 18.55%, respectively. This was closely related to the clear enrichment of Gordonia and its contribution to the increasing abundances of Pararhodobacter, unclassified_f_Cyclobacteriaceae, unclassified_o_Rhodospirillales, Thauera and Candidatus Promineofilum and their associated functional genes that drive P or N removal, thereby enhancing the N and P synergistic degradation efficiency. This study provides a valuable strain resource and process reference for the simultaneously removing N and P from the wastewater.

Study on Plant Growth Promoting Traits of PGPR Isolates From Semi-Arid Kachchh, Gujarat Under Salt Stress Conditions

Salinity is a major problem in the agricultural sector, as it turns productive agronomical land to become unproductive. Therefore, Plant-growth-promoting rhizobacteria (PGPR), that live in the plant root zone named the rhizosphere, is one of the prominent solutions to overcome this problem in an eco-friendly manner as Rhizobacteria responds to osmotic stress and support plant development. Thus, the present study was aimed to characterize various traits of the PGPR strains isolated from saline soils of Kachchh. The characterization of the traits in the presence and absence of sodium chloride was assessed including IAA production (76.97±1.68 mg/l), Ammonia production (38.59±0.19 mg/l), Siderophore production (49.21±1.83%), Phosphate solubilization (4897.73±25.53 mg/l). When assessed for the salt tolerance of the strains in the presence of NaCl between 20-50 gm/L, the strain D6 exhibited a better growth even at 5% NaCl concentration (2.047OD). Further, the effect of PGPR on the growth of V. radiata was 100% in all the experimental setup, whereas in case of B. juncea, the highest germination of 96.67% was observed only in T2 and T1+T2+T3. Further, the molecular sequencing of the strains revealed the identification of the strains as Klebsiella quasipneumoniae, Bacillus paralicheniformis and Klebsiella pneumoniae.

Evaluation of the antiplasmodial efficacy of synthetic 2,5-diphenyloxazole analogs of compounds naturally derived from Oxytropis lanata

The persistent prevalence and dissemination of drug-resistant malaria parasites continue to challenge the progress of malaria eradication efforts. As a result, there is an urgent need to search for and develop innovative therapies. In this study, we screened synthetic 2,5-diphenyloxazole analogs from Oxytropis lanata. Among 48 compounds, 14 potently inhibited the proliferation of P. falciparum strains 3D7 (chloroquine-sensitive) and K1 (multidrug-resistant) in vitro, exhibited IC50 values from 3.38 to 12.65 μM and 1.27–6.19 μM, respectively, and were toxic to human foreskin fibroblasts at 39.53–336.35 μM. Notably, Compounds 31 (2-(2′,3′-dimethoxyphenyl)-5-(2″-hydroxyphenyl)oxazole) and 32 (2-(2′,3′-dimethoxyphenyl)-5-(2″-benzyloxyphenyl)oxazole) exhibited the highest selectivity indices (SIs) against both P. falciparum strains (3D7/K1), with values > 40.20/>126.58 and > 41.27/> 59.06, respectively. In the IC50 speed and stage-specific assays, Compounds 31 and 32 showed slow action, along with distinct effects on the ring and trophozoite stages. Microscopy observations further revealed that both compounds impact the development and delay the progression of the trophozoite and schizont stages in P. falciparum 3D7, especially at concentrations 100 times their IC50 values. In a 72-h in vitro exposure experiment at their respective IC80 in P. falciparum 3D7, significant alterations in parasitemia levels were observed compared to the untreated group. In Compound 31-treated cultures, parasites shrank and were unable to reinvade red blood cells (RBCs) during an extended 144-h incubation period, even after compound removal from the culture. In vivo assessments were conducted on P. yoelii 17XNL-infected mice treated with Compounds 31 and 32 at 20 mg/kg administered once daily for ten days. The treated groups showed statistically significant lower peaks of parasitemia (Compound 31-treated: trial 1 12.7%, trial 2 15.8%; Compound 32-treated: trial 1 12.7%, trial 2 14.0%) compared to the untreated group (trial 1 21.7%, trial 2 28.3%). These results emphasize the potential of further developing 2,5-diphenyloxazoles as promising antimalarial agents.

The Synthesis of 2'-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities.

Chalcones are polyphenols that belong to the flavonoids family, known for their broad pharmacological properties. They have thus attracted the attention of chemists for their obtention and potential activities. In our study, a library of compounds from 2'-hydroxychalcone's family was first synthesized. A one-step mechanochemical synthesis via Claisen-Schmidt condensation reaction under ball mill conditions was studied, first in a model reaction between a 5'-fluoro-2'-hydroxyacetophenone and 3,4-dimethoxybenzaldehyde. The reaction was optimized in terms of catalysts, ratio of reagents, reaction time, and influence of additives. Among all assays, we retained the best one, which gave the highest yield of 96% when operating in the presence of 1 + 1 eq. of substituted benzaldehyde and 2 eq. of KOH under two grinding cycles of 30 min. Thus, this protocol was adopted for the synthesis of the selected library of 2'-hydroxychalcones derivatives. The biological activities of 17 compounds were then assessed against Plasmodium falciparum, Leishmania donovani parasite development, as well as IGR-39 melanoma cell lines by inhibiting their viability and proliferation. Compounds 6 and 11 are the most potent against L. donovani, exhibiting IC50 values of 2.33 µM and 2.82 µM, respectively, better than the reference drug Miltefosine (3.66 µM). Compound 15 presented the most interesting antimalarial activity against the 3D7 strain, with IC50 = 3.21 µM. Finally, chalcone 12 gave the best result against IGR-39 melanoma cell lines, with an IC50 value of 12 µM better than the reference drug Dacarbazine (IC50 = 25 µM).

Metabolic cross-feeding between the competent degrader Rhodococcus sp. strain p52 and an incompetent partner during catabolism of dibenzofuran: Understanding the leading and supporting roles

Microbial interactions, particularly metabolic cross-feeding, play important roles in removing recalcitrant environmental pollutants; however, the underlying mechanisms involved in this process remain unclear. Thus, this study aimed to elucidate the mechanism by which metabolic cross-feeding occurs during synergistic dibenzofuran degradation between a highly efficient degrader, Rhodococcus sp. strain p52, and a partner incapable of utilizing dibenzofuran. A bottom-up approach combined with pairwise coculturing was used to examine metabolic cross-feeding between strain p52 and Arthrobacter sp. W06 or Achromobacter sp. D10. Pairwise coculture not only promoted bacterial pair growth but also facilitated dibenzofuran degradation. Specifically, strain p52, acting as a donor, released dibenzofuran metabolic intermediates, including salicylic acid and gentisic acid, for utilization and growth, respectively, by the partner strains W06 and D10. Both salicylic acid and gentisic acid exhibited biotoxicity, and their accumulation inhibited dibenzofuran degradation. The transcriptional activity of the genes responsible for the catabolism of dibenzofuran and its metabolic intermediates was coordinately regulated in strain p52 and its cocultivated partners, thus achieving synergistic dibenzofuran degradation. This study provides insights into microbial metabolic cross-feeding during recalcitrant environmental pollutant removal.

Dihydrostilbenes from Macaranga javanica (Blume) Müll. Arg. and their antiplasmodial activity

An undescribed dihydrostilbene, macajavanicin D (1), and three known analogs, malayheyneiin A (2) and laevifolins A-B (3-4), were isolated from Macaranga javanica (Blume) Müll. Arg. leaves. Macajavanicin D (1) structure was determined based on a combination of ESI-HRMS data and NMR spectra. Compounds 1-4 were evaluated to Plasmodium falciparum strain 3D7. Macajavanicins D (1) and laevifolin A (3) showed potent activity with an IC50 value of 0.85 and 1.03 µg/mL, respectively.

Nontarget effects of pre‐emergent herbicides and a bioherbicide on soil resources, processes, and communities

Community‐type conversions, such as replacement of perennials by exotic annual grasses in semiarid desert communities, are occurring due to plant invasions that often create positive plant–soil feedbacks, which favor invaders and make restoration of native perennials difficult. Exotic annual grass control measures, such as pre‐emergent herbicides, can also alter soil ecosystems directly or indirectly (i.e. via the plant community), yet there are few studies on the topic in natural, non‐cropped landscapes. We asked how spray treatments applied to soil post‐fire with the intention of inhibiting invasive annual grasses (such as Bromus tectorum L.) and releasing existing native perennial grasses affected soil resources, a microbial process, and invertebrates in three climatically varied sagebrush steppe sites. Spray treatments included chemical herbicides (imazapic and rimsulfuron) that strongly affected plant communities and a bioherbicide (Pseudomonas fluorescens strain D7) that did not. Chemical herbicides increased soil mineral nitrogen in proportion to their negative effects on plant cover for 2 years after treatments in all sites and increased soil water and net N mineralization (measured at one site) but did not affect total carbon, nitrogen, or organic matter. Invertebrate responses to herbicides varied by site, and invertebrates increased with chemical herbicides at the highest, wettest site. We show that herbicide treatments can exacerbate pulses of mineral nutrients, which previous studies have shown can weaken ecosystem resistance to invasion. Thus, restoration strategies that increase the likelihood that desired plants can capture mineralized nutrients after herbicide application will likely be more successful.

Exploration of the catabolic plasmid genes profile of crude oil degrading bacteria isolated from aged oil contaminated soils of Anambra State

This study was undertaken to explore the catabolic plasmid genes profile and molecular identification of crude oil degrading bacteria isolated from aged oil contaminated soils of Anambra State. Enrichment technique, turbidometric test, plasmid profiling and curing tests, biodegradation capability testing as well asmolecular identification method were carried out using standard procedures.A total of sixty (60) bacterial isolates were encountered in the four different soil samples. Of the total bacterial isolates, 22 strains demonstrated high crude oil degrading potentials (A600nm &gt; 0.3). The plasmid DNA was present in 8 out of the 22 bacterial strains such that bacteria strains G2, H4, and K4 had one plasmid each with molecular weight of 9416 base pairs while bacteria strains C3, D1, J3 and L2 had two plasmids each with molecular weight of 2111 base pairs. The bacterial strains C1 and J3 recorded the highest growths on the solid media after the plasmid removal. The isolates belong to various species which are Bacillus cereus C12 (100 % similarity), Pseudomonas aeruginosa KAVK01 (100% similarity), Bacillus licheniformis 126 (96 % similarity), Ochrobacteriumintermedium E85b (97% similarity), Bacillus subtillis SDDlas (100 % similarity), Bacillus subtillis LK4.5 (97 % similarity),Enterobacter cloacae GEBRI III (97 % similarity) and Bacillus cereus So24 (100 % similarity). Therefore, plasmid-borne Pseudomonas aeruginosa and Ochrobacteriumintermediumare recommended for use in bioremediation because of their resilience to the crude oil contaminant and degradation capacities.

Design, synthesis and Anti-Plasmodial activity of Mortiamide-Lugdunin conjugates

In this study, two linear and corresponding cyclic heptapeptide versions of mortiamide A-lugdunin hybrids were designed and synthesized by integrating an anti-malarial peptide epitope derived from Mortiamide A, combined with four residues known for their membrane interactions. Using this synthetic strategy, the sequence of mortiamide A was partly re-engineered with an epitope sequence of lugdunin along with an amino acid replacement using all-L and D/L configurations. Importantly, the re-engineered cyclic mortiamides with all-L (3) and D/L (4) configurations exhibited promising anti-malarial activities against the P. falciparum drug-sensitive TM4/8 strain with half-maximal inhibitory concentration (IC50) values of 6.2 ± 0.5 and 4.8 ± 0.1 μM, respectively. Additionally, they exhibited anti-malarial activities against the P. falciparum multidrug-resistant V1/S strain with IC50 values of 5.0 ± 2.6 and 3.7 ± 0.7 μM, respectively. Interestingly, a linear re-engineered mortiamide with D/L configuration (2) exhibited promising anti-malarial activities, surpassing those of the re-engineered cyclic mortiamides (3 and 4), against both the P. falciparum sensitive TM4/8 and multidrug-resistant V1/S strains with IC50 values of 3.6 ± 0.5 and 2.8 ± 0.7 μM (IC50 of Mortiamide A = 7.85 ± 0.97, 5.31 ± 0.24 μM against 3D7 and Dd2 strains) without any cytotoxicity at >100 µM. The presence of D/L forms in a linear structure significantly impacted the anti-malarial activity against both the P. falciparum sensitive TM4/8 strain and the multidrug-resistant V1/S strain.