Spiral molecules with antimalarial activities: A review

The medicinal chemistry and drug development of novel antimalarials.

Background: Heterocyclic compounds are particularly important in medicinal chemistry. With a range of therapeutic uses, benzimidazoles and quinolines are both key heterocycles in medicinal chemistry. A number of hybrid heterocyclic compounds have been reported in recent years because they typically have better therapeutic properties than single heterocyclic rings. Methods: A literature search was conducted across relevant scientific literature from peer-reviewed sources, using keywords, including “benzimidazole”, “quinoline”, “benzimidazole-quinoline hybrids”, “antibacterial”, “antifungal”, “antimalarial” and “hybrid complexes”. Results: This review summarizes the synthetic methodologies for benzimidazole–quinoline hybrids, benzimidazole– quinolinones, and benzimidazole–quinoline metal complexes, along with their antimicrobial and antimalarial activities and the reported structure–activity relationship (SAR) studies. The importance of halogen substitution, particularly with chlorine and fluorine atoms, as well as the structure of the linker between the benzimidazole and quinoline rings—specifically chain length, the presence of oxygen, sulfur, or nitrogen atoms, and heterocyclic moieties—is highlighted. A series of benzimidazole–quinoline hybrids exhibit antimalarial and antitrypanosomal activities or show enhanced antimicrobial properties due to the incorporation of a five-membered heterocycle in addition to the two existing heterocyclic rings. Notably, several hybrids from different compound series exhibit very low minimum inhibitory concentrations (MICs) in the range of 1–8 µg/mL, along with low cytotoxicity, supporting their potential for further investigation as antimicrobial agents. Conclusions: This review summarizes the synthetic methods, medicinal properties, and structure–activity relationship (SAR) studies of benzimidazole–quinoline hybrids reported between 2002 and 2026.

Leishmaniasis and malaria are serious public health problems in tropical and sub-tropical regions worldwide. Development of drug-resistant strains has disrupted efforts to control the spread of these diseases in the world. The conventional antiparasitic chemotherapy still suffers from side effects and drug resistance. Therefore, the development of novel antimalarial and leishmanicidal drugs remains a critical topic to combat against these diseases. Five-membered heterocyclic systems have possessed antiparasitic activity such as thiadiazole scaffold which is a prevalent and an important heterocyclic ring. For this purpose, the authors introduce a series of synthetic thiadiazole derivatives with antileishamanial activity. Also, the authors searched a number of sources and articles to find thiadiazole derivatives with antileishamnial and antimalarial activity. Then all of the findings were reviewed. 5-nitroheteroaryl-1,3,4-Thiadiazole derivatives with different substituents at position 2 of the thiadiazole ring (8, 10-11) presented the best antileishmanial activity with low toxicity compared with reference drug. Also, 1,3,4-thiadiazole-2-sulfonamide derivative (18) showed excellent inhibitory activity against pfCA as a special enzyme in Plasmodium falciparum. Thiadiazole scaffold has the suitable physicochemical and pharmacokinetic properties and still stays as a therapeutic target for the development of a novel lead in the medicinal chemistry. Therefore, the current review provides a brief summary of medicinal chemistry of thiadiazole ring and introduces novel leads possessing this nucleus with antimalarial and antileishmanial activities.

Yield Production and Energy Budget of Traditional Agricultural Crops in Garhwal Himalaya

Malaria remains a major public health problem in the tropical and subtropical regions. This study aimed of investigating the antimalarial and antioxidant activities of ethanol extract of Lophira lanceolata stem bark. Methodology. The antimalarial activity was determined using the Peter 4-days' suppressive and Rane's curative tests on Swiss albino: these mice were infected with 1 × 107 parasitized red blood cells. The percentage reduction of parasitemia was related to each test, and the liver homogenate was used to assay malondialdehyde, superoxide dismutase, nitrogen monoxide, catalase, and glutathione for the evaluation of oxidative stress. During the curative test, blood was collected for hematological parameters, alanine aminotransferase and aspartate aminotransferase to evaluate liver function. The ethanol extract of L. lanceolata showed a dose-dependent suppressive activity with the highest suppression of 88.22% at 500 mg/kg. Suppression produced by the extract was not significantly higher than that of the reference drug with 96.1%. Similarly, the extract at doses 125, 250, and 500 mg/kg showed significant decreases (P < 0.05) in a dose-dependent manner during the curative test. The ethanol extract of L. lanceolata caused a reduction of tissue markers, such as hepatic oxidative stress, as it increased the enzymatic activity of antioxidant enzymes. The ethanol extract of L. lanceolata possesses both antimalarial and antioxidant activities. However, further in vivo toxicity tests are required to guarantee their safety.

BackgroundThe northern part of India harbours a great diversity of medicinal plants due to its distinct geography and ecological marginal conditions. The traditional medical systems of northern India are part of a time tested culture and honored still by people today. These traditional systems have been curing complex disease for more than 3,000 years. With rapidly growing demand for these medicinal plants, most of the plant populations have been depleted, indicating a lack of ecological knowledge among communities using the plants. Thus, an attempt was made in this study to focus on the ecological status of ethnomedicinal plants, to determine their availability in the growing sites, and to inform the communities about the sustainable exploitation of medicinal plants in the wild.MethodsThe ecological information regarding ethnomedicinal plants was collected in three different climatic regions (tropical, sub-tropical and temperate) for species composition in different forest layers. The ecological information was assessed using the quadrate sampling method. A total of 25 quadrats, 10 × 10 m were laid out at random in order to sample trees and shrubs, and 40 quadrats of 1 × 1 m for herbaceous plants. In each climatic region, three vegetation sites were selected for ecological information; the mean values of density, basal cover, and the importance value index from all sites of each region were used to interpret the final data. Ethnomedicinal uses were collected from informants of adjacent villages. About 10% of inhabitants (older, experienced men and women) were interviewed about their use of medicinal plants. A consensus analysis of medicinal plant use between the different populations was conducted.ResultsAcross the different climatic regions a total of 57 species of plants were reported: 14 tree species, 10 shrub species, and 33 herb species. In the tropical and sub-tropical regions, Acacia catechu was the dominant tree while Ougeinia oojeinensis in the tropical region and Terminalia belerica in the sub-tropical region were least dominant reported. In the temperate region, Quercus leucotrichophora was the dominant tree and Pyrus pashia the least dominant tree. A total of 10 shrubs were recorded in all three regions: Adhatoda vasica was common species in the tropical and sub-tropical regions however, Rhus parviflora was common species in the sub-tropical and temperate regions. Among the 33 herbs, Sida cordifolia was dominant in the tropical and sub-tropical regions, while Barleria prionitis the least dominant in tropical and Phyllanthus amarus in the sub-tropical region. In temperate region, Vernonia anthelmintica was dominant and Imperata cylindrica least dominant. The consensus survey indicated that the inhabitants have a high level of agreement regarding the usages of single plant. The index value was high (1.0) for warts, vomiting, carminative, pain, boils and antiseptic uses, and lowest index value (0.33) was found for bronchitis.ConclusionThe medicinal plants treated various ailments. These included diarrhea, dysentery, bronchitis, menstrual disorders, gonorrhea, pulmonary affections, migraines, leprosy. The ecological studies showed that the tree density and total basal cover increased from the tropical region to sub-tropical and temperate regions. The species composition changed with climatic conditions. Among the localities used for data collection in each climatic region, many had very poor vegetation cover. The herbaceous layer decreased with increasing altitude, which might be an indication that communities at higher elevations were harvesting more herbaceous medicinal plants, due to the lack of basic health care facilities. Therefore, special attention needs to be given to the conservation of medicinal plants in order to ensure their long-term availability to the local inhabitants. Data on the use of individual species of medicinal plants is needed to provide an in-depth assessment of the plants availability in order to design conservation strategies to protect individual species.

The increase of fossil‐fuel burning and nitrogen (N) fertilizer consumption continues to elevate global N deposition, leading to significant increases of soil NH 4 + and NO 3 − concentrations, and thus N 2 O emissions. This is especially important for natural, unmanaged soils which are considered as areas that are sensitive to N input. However, uncertainties exist regarding the interactions of soil N 2 O emissions with soil NH 4 + and NO 3 − concentrations in response to N input in different climatic regions, as well as their underlying potential mechanisms. Here, we conducted a meta‐analysis to investigate the responses of these three forms of N to external N input across global natural ecosystems, using data extracted from peer‐reviewed studies. The results show that soil NO 3 − concentrations are increased to a much larger extent by N input in temperate regions (136%) compared to tropical (62%) and subtropical (54%) regions, whereas the increase of soil NH 4 + concentrations by N input is much less than soil NO 3 − concentrations, at 20%, 26% and 28% in temperate, tropical and subtropical regions, respectively. The significantly larger increase in soil NO 3 − concentrations but slightly lower increase in soil NH 4 + concentrations in temperate regions compared to other climatic zones may be ascribed to the dominant nitrification process in temperate areas, which promotes the conversion of NH 4 + to NO 3 − . Soil N 2 O emissions were increased to the greatest extent in subtropical regions (348%) in response to N input, followed by temperate regions (111%) and tropical regions (44%), which may be a result of the dominant denitrification process in subtropical regions, which promotes N 2 O production. It is likely that denitrification also dominates N 2 O production in tropical regions, but the dampened effect of N input on stimulating soil N 2 O emissions in these areas suggests that the loss of NO 3 − substrate due to intensive leaching might be an important issue. This study could provide a better understanding of the heterogeneous risks of soil N responses in different climatic zones in the context of increasing global N deposition. Highlights Larger N input‐induced increases in soil NO 3 − concentrations in temperate regions may derive from increased nitrification. Larger N input‐induced increases in soil N 2 O emissions in subtropical regions may derive from increased denitrification. Less increase in soil N 2 O emissions in tropical regions after N input may be due to heavy precipitation‐induced NO 3 − leaching. Soil N 2 O emissions in subtropical regions may be more sensitive to increased N input compared to other climatic zones.

Biases in shortwave cloud radiative forcing (SWCF), which cause overestimates in tropical regions and underestimates in subtropical marine stratocumulus regions, are common in many climate models. Here, two boundary layer processes are investigated in the atmospheric model GAMIL2, entrainment at the top of the boundary layer and longwave radiative cooling at the top of stratocumulus clouds, in order to reduce biases and reveal the mechanisms underlying these processes. Our results show that including the entrainment process in the model can reduce negative SWCF biases in most tropical regions but increases positive SWCF biases in subtropical marine stratocumulus regions. This occurs because entrainment reduces the low-level cloud fraction and its cloud liquid water content by suppressing the vertical turbulent diffusion in the boundary layer and decreasing the relative humidity when warm and dry free atmosphere is entrained in the boundary layer. Longwave radiative cooling at the top of stratocumulus clouds can enhance turbulent diffusion within the stratocumulus-topped boundary layer. When combined with the entrainment process, longwave radiative cooling reduces the positive SWCF biases in subtropical marine stratocumulus regions that are observed using the entrainment process alone. The incorporation of these two boundary layer processes improves the simulated SWCF in tropical and subtropical regions in GAMIL2.

Malaria is an infectious disease, endemic to tropical and sub-tropical regions causing half a million people's deaths every year. Bioactive compounds derived from medicinal plants are used to treat malaria disease and its complications. H. cannabinus and C. capsularis are two edible medicinal plants widely cultivated throughout the state of Assam in India. In this study, in-vitro and in-silico investigations were performed to explore the anti-malarial activity of the plant extracts against Plasmodium falciparum with its validation of hemocompatibility on human RBC. We report H. cannabinus and C. capsularis extracts possess highly potent antimalarial activity against Plasmodium falciparum with IC50 values of 3.80 ±0.3 and 7.90 ±0.8 µg/mL, respectively. The plant extracts showed growth inhibition of A549 lung adenocarcinoma cells, no toxicity on non-cancerous Vero cells, and no hemolytic activity on human RBCs. The GC-MS analysis detected bioactive compounds 2-pyrazoline-3-carboxylic acid; 5-hydroxy-1-(4-methyl benzoyl)-5-phen 5-oxo-1-phenyl-4H-pyrazole-3-carboxylic acid; 9-oximino-2,7-diethoxyfluorene; and nonane-diamide, n, n'-di-benzoyloxy in H. cannabinus; and, (+)-sesamin; tetrahydropyran-4-carboxylic acid, 4-phenyl-, (3-chloro-4-methylphenyl; and safrole in C. capsularis. In in-silico study, antimalarial compounds in the extracts were predicted to have good binding affinities with docking score of <-7.5kcal/mol on Falcipain-2, and Cytchrome c2 proteins that promotes thegrowth and invasion of P. falciparum.

Chemical study, antimalarial and antioxidant activities, and cytotoxicity to human breast cancer cells (MCF7) of Argania spinosa

Malaria is one of the major infectious diseases and foremost cause of mortality and morbidity in many subtropical and tropical regions. In the last years, the situation has become worst in many ways, due to increase in the parasites resistance to various available antimalarial agents. Furthermore, malaria`s control is beginning to be more sophisticated by the parallel spread of mosquito vector`s resistance to the available insecticides. Recently, there is a wide consensus to seek for target specific, safe, affordable, and effective new antimalarial agents, which can compete with synthetic ones. Endophytic fungi are of a growing interest as prominent sources of structurally unique bioactive natural products. The bio-metabolites isolated from endophytic fungi, possessing antimalarial potential may compose the base for the synthesis of novel drugs that might be utilized to withstand malaria and its resistance. For getting information on the various studies, PubMed, Google Scholar, ScienceDirect, SpringerLink, Scopus, and Wiley search was done using keywords (malaria, endophytic fungi, and antimalarial activity). The present review covers the literature published from 1996 to 2017 and highlights the metabolites for which antimalarial activities have been reported. Overall, 135 fungal metabolites and 72 references are cited. In addition, their structure, chemical class, fungal source, host, and activity have been presented. This review shows the significance of endophytic fungi as a wealthy pool of antimalarial agents.

Our aim was to test if ecological stages may influence the arbuscular mycorrhizal fungi (AMF), nematodes, and the soil chemical properties in agroforestry systems (AF), unassisted forest restoration (UFR), and natural ecosystem (Ne) located in the Brazilian Tropical and Subtropical regions. We collected soil samples to determine AMF, nematodes, soil pH, P, and soil organic carbon (SOC). AMF and nematode richness in the AF and Ne were similar in the tropical region. The redundancy analysis (RDA) indicated that the abundance of AMF and soil nematodes was mainly affected by soil pH, P, and SOC. Differences were associated with (1) ecological stages, as we found differences in AMF and nematode abundance as affected by habitat simplification, and (2) changes in soil pH, SOC, and P. Our work increases the understanding of the AMF and soil nematode community in the rhizosphere of AF and Ne in tropical and subtropical regions.

The use of fuel wood in the Garhwal Himalaya as a primary source of energy for domestic purposes is causing severe deforestation in the Garhwal Himalaya. The fuel wood consumption patterns have been studied in six villages selected two each in tropical (Ganga Bhogpur and Kunow), sub-tropical (Bhainswara and Ghargaon) and temperate (Dhaulana and Chunnikhal) regions under various ecological and socio-economic conditions. The highest value of total fuel wood consumption for various purposes was observed for the village Ganga Bhogpur (907.20 kg capita-1 yr-1) in the tropical region, whereas, it was lowest for the village Ghargoan (586.8 kg capita-1 yr-1) in the sub-tropical region. The labour energy expenditure for fuel wood collection was maximum in the village Dhaulana (53516.30 MJ person-1 yr-1) in temperate region, which was due to the distance from the forest recorded as 1.0 km and was higher compared to others. The terrain which has a steep slope consumed maximum time for fuel wood collection while, minimum was in village Ganga Bhogpur (32412.00 MJ capita-1 yr-1) in the tropical region, which could be due to nearness of the village to the forest (0.40 km) and was also more convenient for villagers to go for fuel wood collection. Fuel wood consumption also fluctuated with the season as reported to be higher in winter>rainy>summer. The tree and shrub species preferred by the inhabitants for fuel wood were Holoptelea integrifolia, Anogeissus latifolia and Lantana camara in tropical region; Anogeissus latifolia, Acacia catechu and Carissa spinarum in sub-tropical region; and Quercus leucotrichophora, Myrica esculenta and Pyracantha crenulata in temperate region. Keywords: Fuel wood consumption, altitudes, Garhwal Himalaya, season Journal of Environmental Extension Vol. 7 2008: pp. 16-22

Fuelwood consumption pattern at different altitudes in rural areas of Garhwal Himalaya

Background: Malaria is an infectious disease caused by the Plasmodium parasite and transmitted by the Anopheles mosquito. Plasmodium falciparum is a parasite that causes the most deaths. Currently, there is resistance to various antimalarial drugs. For this reason, it is necessary to search for new antimalarial agents. Medicinal plants have been shown to play an important role in treating malaria for thousands of years. Some of Euphorbiaceae family plants contains terpenoid compounds, which are compounds with antimalarial activity. Objective: The present review aims to provide an overview of the terpenoid compounds from Euphorbiaceae family as an antimalarial. Method: Comprehensive information on Euphorbiaceae family from 2002-2022 was searched for literature relevant to major science-based data, including Scopus, Science, ScienceDirect, Pubmed, and SciFinder, using appropriate keyword combinations. Result: A total of 15 papers were included in this review. The terpenoids isolated from 14 species of Euphorbiaceae family and reported to possess antimalarial activity are presented. Conclusion: Terpenoids are found in almost all parts of Euphorbiaceae family plants and are reported to have moderate to high antimalarial activity. Screening of antimalarial terpenoid activity in Ephorbiaceae family plants can be a key step in the source and development of new antimalarial drugs.