1,2,3-Triazolyl-tetrahydropyrimidine Conjugates as Potential Sterol Carrier Protein-2 Inhibitors: Larvicidal Activity against the Malaria Vector Anopheles arabiensis and In Silico Molecular Docking Study.

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis, a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure-activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules' potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis, 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.

Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria Vector Anopheles arabiensis, In Silico ADMET Prediction and Molecular Target Investigation.

Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand. In order to identify new potential larvicidal agents, a series of 2-aryl-1,2-dihydroquinazolin-4-one derivatives were synthesized and evaluated for their larvicidal activity against Anopheles arabiensis. The in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were also investigated and most of the derivatives possessed a favorable ADMET profile. Computational modeling studies of the title compounds demonstrated a favorable binding interaction against the acetylcholinesterase enzyme molecular target. Thus, 2-aryl-1,2-dihydroquinazolin-4-ones were identified as a novel class of Anopheles arabiensis insecticides which can be used as lead molecules for the further development of more potent and safer larvicidal agents for treating malaria.

Redescription of immatures of Dasyhelea flavifrons Guérin-Méneville (Culicomorpha: Ceratopogonidae) and new contribution to the knowledge of its larval habitats.

The fourth instar larva and pupa of Dasyhelea flavifrons Guérin-Méneville are redescribed, illustrated, and photomicrographed using binocular, phase-contrast, and scanning electron microscopy. Comparisons with the American species of the grisea group were made. The immatures were collected by using a siphon bottle in tree-holes and from water collected in dead snail shells in Salta Province, Argentina, transported to the laboratory and there bred to the emergence of the adults. Details on larval habitats are given. These are the first records from Argentina and in gastrotelmata.

Evaluation of halogenated coumarins for antimosquito properties.

Mosquitoes are the major vectors of parasites and pathogens affecting humans and domestic animals. The widespread development of insecticide resistance and negative environmental effects of most synthetic compounds support an interest in finding and developing alternative products against mosquitoes. Natural coumarins and synthetic coumarin analogues are known for their several pharmacological properties, including being insecticidal. In the present study halogenated coumarins (3-mono/dibromo acetyl, 6-halogenated coumarin analogues) were screened for larvicidal, adulticidal, and repellent properties against Anopheles arabiensis, a zoophilic mosquito that is one of the dominant vectors of malaria in Africa. Five compounds exerted 100% larval mortality within 24 h of exposure. All coumarins and halogenated coumarins reversibly knocked down adult mosquitoes but did not kill them after 24 h of exposure. Repellent properties could not be evidenced. Five compounds were considered potential larvicidal agents for further research and development, while adulticidal activity was considered only mild to moderate.

Mosquito communities in Nova Iguaçu Natural Park, Rio de Janeiro, Brazil.

ABSTRACT. In order to gather information on the culicid fauna of Nova Iguaçu Municipal Park, Rio de Janeiro, Brazil, adult and immature stages were collected with the Centers for Disease Control and Prevention miniature light traps, and dippers and suction tubes, respectively. In all, 828 adult and 990 immature specimens were collected belonging to 12 genera. Among the species collected were Aedes aegypti, Ae. albopictus, Ae. fluviatilis, Ae. scapularis, Haemagogus leucocelaenus, and Psorophora ferox that are considered of potential medical importance. Culicids used a variety of larval habitats and bred under diverse ecological conditions, mostly in natural water containers formed by bamboo, bromeliad, ground depression, rock pool, stream, tree hole, and in artificial containers such as abandoned bathtub, car carcass, abandoned sink, plastic cup, waste tire, and water tank. Species richness and diversity increased from lower to higher forest cover and was highest in sites with highest diversity and high number of larval habitats.

Urban landscape as a determinant of sarcosaprophagous fly assemblages of sanitary interest: a comparative field study between larviparous and oviparous reproductive strategies.

In Diptera, reproductive strategies vary according to the stage of development of the newly deposited offspring and their abundance. The aim of our study is to establish connections between the reproductive strategies of flies (larviparous or oviparous) and the prevailing local conditions (sun or shade) as well as landscape attributes (low or high urbanization) in an urban setting. We collected flies using 2 baited traps (in the sun or shade) at each of the 13 study sites with varying levels of urbanization. We used generalized linear mixed models to examine the impact of landscape and local characteristics on the diversity (abundance and richness of larviparous and oviparous Diptera) of sarcosaprophagous flies. Our findings indicate that while the abundance and diversity of both larviparous and oviparous flies are affected by urbanization, larviparous flies would be less sensitive to more urbanized environments. Larviparous also exhibit a preference for resources under sun exposure, while the responses of oviparous seem more species-dependent. The observed patterns can be explained by the known biology of the studied groups.

Aedes aegypti oviposition dynamics in towns with low human population density in yungas and dry chaco, Salta, Argentina.

We assessed the presence of Aedes aegypti in five ecorregions of Salta province and compared the oviposition activity of Ae. aegypti using ovitraps in towns of two contrasting ecoregions (yungas and Chaco dry forests) in the province of Salta, Argentina, a major contrast in these ecoregions are rain patterns and altitude. Our aim was to estimate how oviposition activities were associated with the ecoregion and site scale local environmental variables. Mosquito oviposition activity was monitored weekly during the summer using ovitraps. Predictor variables were ecoregion, town, and meteorological variables. The effect of the predictor variables was measured on the response variables using multi-model inference. Besides yungas, the presence of Aedes aegypti was confirmed in towns of dry Chaco and High Monte. The only factor that had a significant effect on the presence of eggs in the ovitraps was the ecoregion, with the frequency of positives being higher in yungas. For the number of eggs, the ecoregion, the night temperature of the first week and the NDVI would explain said variable. Overall, results indicate that the variations between towns would be more related with their ecological and climatic characteristics than with the more immediate meteorological variations.

Synthesis, characterization and larvicidal studies of ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues against Anopheles arabiensis and cheminformatics approaches.

According to WHO, in 2021, there was an estimation of 247 million malaria cases from 84 malaria-endemic countries. Globally an estimated count of 2 billion malaria cases and 11.7 million deaths due to malaria were recorded in the past two decades. Further, the emergence of drug-resistant mosquitos threatens mankind. Therefore, the development of newer larvicidal agents is the need of the hour. This research identifies a new series of variably substituted indolizines for their effectiveness in controlling Anopheles arabiensis larvae through larvicidal activity. The series of Ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues (4a-j) were synthesized by reacting 4-(piperidin-1-yl)pyridine, phenacyl bromides with ethyl propiolate via 1, 3-dipolar cycloaddition and the green metrics of the process are reported. All the newly synthesized compounds were characterized by spectroscopic techniques such as 1H NMR,13C NMR, FT-IR, and HRMS. The larvicidal effectiveness of the newly synthesized compounds was assessed against Anopheles arabiensis. Among the compounds studied, namely 4c, 4d, 4e, and 4f, displayed the most notable larval mortality rates within the series, reaching 73%, 81%, 76%, and 71% respectively, in contrast with the negative control acetone. In comparison, the standard Temephos exhibited a mortality rate of 99% at the same concentration. Furthermore, computational approaches including molecular docking and molecular dynamics simulations identified the potential targets of the series compounds as the larval Acetylcholinesterase (AChE) enzyme and the Sterol Carrier Protein-2 (SCP-2) protein. However, it is essential for these computational predictions to undergo experimental validation.Communicated by Ramaswamy H. Sarma.

Damselflies (Coenagrionidae) have been avoiding leaf veins during oviposition for at least 52 million years.

Plant-insect interactions can provide extremely valuable information for reconstructing the oviposition behavior. We have studied about 1350 endophytic egg traces of coenagrionid damselflies (Odonata: Zygoptera) from the Eocene, identifying triangular or drop-shaped scars associated with them. This study aims to determine the origin of these scars. Our behavioral study of about 1,800 endophytic eggs from recent coenagrionids indicates that these scars were caused by ovipositor incisions, but without egg insertion. The scar correlates (χ2-test) with leaf veins in both fossil and extant species. We infer that a female would detect the proximity of a leaf vein and avoid egg-laying, generating a scar that also fossilizes. For the first time, a scar produced by the ovipositor has been identified, indicating the existence of undesirable areas for oviposition. Accordingly, we recognize that Coenagrionidae damselflies (narrow-winged damselflies or pond damselflies) have been avoiding leaf veins for at least 52 million years.

Synthesis, biological evaluation, and computational investigation of ethyl 2,4,6-trisubstituted-1,4-dihydropyrimidine-5-carboxylates as potential larvicidal agents against Anopheles arabiensis.

Malaria is one of the most known vector-borne diseases caused by female Anopheles mosquito bites. According to WHO, about 247 million cases of malaria and 619,000 deaths were estimated worldwide in 2021, of which 95% of the cases and 96% of deaths occurred in the African region. Sadly, about 80% of all malaria deaths were of children under five years old. Despite the availability of different insecticides used to control this disease, the emergence of drug-resistant mosquitoes threatens public health. This, in turn, highlighted the need for new larvicidal agents that are effective at different larval life stages. This study aimed to identify novel larvicidal agents. To this end, a series of ethyl 2,4,6-trisubstituted-1,4-dihydropyrimidine-5-carboxylates 8a-i was synthesized using a three-step chemical synthetic approach via a Biginelli reaction employed as a key step. All title compounds were screened against Anopheles arabiensis to determine their larvicidal activities. Among them, two derivatives, ethyl 2-((4-bromophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8b and ethyl 2-((4-bromo-2-cyanophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8f, showed the highest larvicidal activity, with mortality of 94% and 91%, respectively, and emerged as potential larvicidal agents. In addition, computational studies, including molecular docking and molecular dynamics simulations, were carried out to investigate their mechanism of action. The computational results showed that acetylcholinesterase appears to be a plausible molecular target for their larvicidal property.Communicated by Ramaswamy H. Sarma.

Use of Aedes aegypti Oviposition Surveillance and a Geographic Information System for Planning Anti-Vectorial Measures.

Arboviruses transmitted by Aedes aegypti pose a threat to global public health. Because there are no vaccines or drugs available, the prevention of these diseases in Argentina is based on integrated vector control. In this work, the spatiotemporal dynamics of the vector distribution was analyzed by monitoring oviposition. This information allowed the planning of anti-vector interventions and the evaluation of their effect on the relative abundance of mosquito populations in San Ramón de la Nueva Orán. Observed data were compared with the eggs expected via a statistical model based on meteorological variables. The oviposition substrate preference of mosquito females was also evaluated, and the possible relationship between the relative abundance of the vector and sociodemographic and environmental variables (normalized difference vegetation index and normalized difference water index) was explored. A total of 4,193 eggs of Ae. aegypti were collected, and spatial clusters were detected for all months for which the presence of the mosquito was reported. The observed number of eggs was significantly less than the expected-corrected egg abundance. A significant correlation of oviposition activity was found with three sociodemographic variables, whereas no significant correlation was found with mean or median values of the environmental variables studied. This monitoring strategy made it possible to address the interventions and evaluate them, proposing them as good complementary tools for the control of Ae. aegypti in northern Argentina.

Repellence of essential oils of aromatic plants growing in Argentina against Aedes aegypti (Diptera: Culicidae).

Mosquitoes are vectors of pathogens to humans and domestic animals and may also have economical impacts. One approach to prevent mosquito-borne diseases is bite deterrence through the application of repellents. Currently, there is an interest to search for alternative bioactive products to the synthetic active ingredients most widely used in insect repellents. Repellence against Aedes aegypti of essential oils extracted from Acantholippia salsoloides, Aloysia catamarcensis, Aloysia polystachya, Lippia integrifolia, Lippia junelliana (Verbenaceae), Baccharis salicifolia, Euphatorium buniifolium, and Tagetes filifolia (Asteraceae) were assessed. Tests were conducted by alternatively exposing untreated and treated forehand to the mosquitoes and counting probing attempts. All essential oils tested were significantly repellent against A. aegypti when compared to untreated controls; L. junelliana was the most repellent and T. filifolia was the least based on the response of the mosquitoes to different concentrations of the essential oils (EO). Repellence may be attributed to the respective main components of each EO.

Scanning electron microscopy of the eggs of Aedes scapularis from southern South America.

The eggs of Aedes scapularis analyzed by scanning electron microscopy are black and elliptical in outline, measuring approximately 620.4 +/- 16.74 microm long and 163.7 +/- 16.90 microm (n = 10) wide, with an egg index (length/width ratio) of 3.79. The anterior extremity tapered abruptly from a width of 51.6 microm, while such tapering was more gradual at the posterior extremity, from a width of 61.4 microm. The ventral surface of the chorionic coating presented cells with a tubular aspect containing tubercles in rows at a density of 5 to 9 per cell with 2 different sizes, the largest measuring 7.23 +/- 0.98 microm in a longitudinal diameter and the smallest 4.15 +/- 0.53 microm (n = 30). In the dorsal region, the external chorionic reticulum had a porous appearance, and its thickness ranged from 2.5 to 4.1 microm. Isolated tubercles presented wide variation per cell. In the central region of some chorionic cells were tubercles of greater diameter, characterized as central tubercles of 8.45 +/- 0.67 microm, and around them 3 to 5 smaller tubercles measuring 2.57 +/- 0.26 microm. The micropylar apparatus presented a collar with a very evident molding and edges with defined margins for the transition area and a thickness of around 11.1 microm. The micropyle disc margins were raised, measuring around 17.8 microm in diameter and 229 microm in circumference. The micropyle orifice was very evident, with a diameter of 1.41 microm.

Geometric morphometrics of endophytic oviposition traces of Odonata (Eocene, Argentina).

The insertion of the Odonata ovipositor in the plant tissue generates a scar that surrounds the eggs (trace). In insects, individual egg traces are known to vary in size, but their variation in individual shape is mostly unknown. Twenty-four specimens were obtained from the Laguna del Hunco (Lower Eocene, Chubut) and Río Pichileufú (Middle Eocene, Río Negro), Argentina, which had 1346 oviposition traces (MEF Collection). For the first time, a study of the shape and size of a large number of individual Odonata endophytic egg traces was carried out using traditional (general and mixed linear models) and geometric morphometrics (Fourier elliptical series) to elucidate whether there are changes in size or shape of the individual endophytic egg traces associated with the substrate used at the time of oviposition, if the Lower Eocene traces have varied in relation to those of the Middle Eocene, and if the ichnological classification (Paleoovoidus arcuatus, P. bifurcatus and P. rectus) reflects such variations. We found differences in size (p < 0.05), but not in shape, in relation to the variables studied. This could reflect that the shape of Odonata eggs (inferred from the traces), unlike their size, could have a strong evolutionary constraint already observed since the Eocene.

Scanning electron microscopy of the egg of Ochlerotatus albifasciatus (Diptera: Culicidae).

Ochlerotatus albifasciatus (Macquart) (Diptera: Culicidae) is a mosquito species of medical and veterinary importance, usually associated with temporary groundwater habitats. Eggs obtained from females collected in Córdoba city, in the center of Argentina, were studied using scanning electron microscopy. The eggs are elliptical in outline, measuring approximately 615.7 +/- 37.24 microm in length (1) and 180.7 +/- 22.87 microm in width (w), with an egg index (l/w ratio) of 2.9-3.7. The outer chorionic sculpture has racquet-shaped and wristwatch-shaped cells consisting of a small central tubercle surrounded by larger tubercles and followed by a row of smaller tubercles on one or both sides, respectively, although variations between regions of the egg were observed. The micropylar apparatus has a collar with evident molding and edges of determined length, albeit irregular, with defined margins for the transition area and a thickness of approximately 10.7 microm. The margins of the micropylar disc are raised and the disc measures approximately 21.1 microm in diameter. The micropyle is distinct.

Effects of the essential oils of Lippia turbinata and Lippia polystachya (Verbenaceae) on the temporal pattern of locomotion of the mosquito Culex quinquefasciatus (Diptera: Culicidae) larvae.

The essential oils (EO) of Lippia turbinata (TUR) and Lippia polystachya (POL) have shown lethal effects against mosquito larvae. The present work evaluated whether these EO at doses ranging from sublethal to lethal (20, 40 and 80 ppm) modify the temporal pattern of locomotion of Culex quinquefasciatus larvae. Larvae were individually placed in glass boxes, and their activity recorded at 0.3 s intervals during 40 min. Individuals treated with doses >40 ppm of either EO significantly decreased their ambulation speed and the percentage of total time ambulating compared to controls. TUR 80 ppm decreased their ambulation even sooner than POL 80 ppm, when compared to their respective controls. These findings are consistent with the neurotoxic effect against insects attributed to alpha-Thujone, a main component of both EO. A detrended fluctuation fractal analysis evaluating the complexity and organisation of the temporal pattern of locomotion showed fractal patterns in all animals. Both sublethal and lethal doses of TUR and POL increased the complexity of ambulation. Interestingly, for POL 20 ppm, an increase in complexity was observed, while no changes in general activity were detected, suggesting that fractal analysis may be more sensitive to detect behavioural changes than general activity evaluation.

First record of Culex (Melanoconion) pilosus from Cordoba City, Argentina.

Larvae of Culex (Melanoconion) pilosus were collected in February 2006 during a survey of mosquito fauna inhabiting water bodies in an urban environment in Córdoba city. This is the 1st record of the species in this locality of Argentina, the most western report of this species in the Chaco phytogeographic region.

Vegetation Cover and Microspatial Distribution of Sand Flies (Diptera: Psychodidae) in an Endemic Locality for Cutaneous Leishmaniasis in Northern Argentina.

The sand fly fauna in Hipólito Yrigoyen, Argentina, a locality where cutaneous leishmaniasis cases occur, was surveyed with zones of higher abundance of sand flies correlated to vegetation cover estimated through normalized difference vegetation index (NDVI). Sand flies were collected with 10 CDC traps during six nights, from December 2009 to January 2010. A map was built of expected sand flies abundance in which levels of NDVI were categorized. In total, 1,392 Phlebotominae (Diptera: Psychodidae) specimens were collected, comprised of the following species: Nyssomyia neivai (Pinto 1926), Migonemyia migonei (França 1920), species of the cortelezzii complex (Brèthes 1923), Evandromyia sallesi (Galvão & Coutinho 1940), and Psathyromyia shannoni (Dyar 1929). Positive correlations were found between the abundance of sand flies and the NDVI (P < 0.05) for buffer areas of <150 m radii from the trap location points, i.e., the sand fly abundance was greater where vegetation cover and density were greater. In this context, plant cover should be taken into account to prioritize surveillance and control areas within the program of sand flies control in northern Argentina.

Distribution of Haemagogus and Sabethes Species in Relation to Forest Cover and Climatic Factors in the Chapada Dos Guimarães National Park, State of Mato Grosso, Brazil.

Members of the genera Haemagogus and Sabethes are the most important biological vectors of the wild yellow fever virus (WYF) in the forested areas of the Americas. The ecologies of Haemagogus janthinomys, Hg. leucocelaenus, Sabethes chloropterus, and Sa. glaucodaemon were studied in a forest of the Chapada dos Guimarães National Park, state of Mato Grosso, Brazil, to evaluate the influence of climatic factors (temperature and relative humidity [RH]) on their abundance. We also examined the association of climate with landscape structure on species distribution patterns throughout the seasons of the year. Multiple stepwise regressions showed that RH was most likely to influence the density of mosquito populations. A multidimensional scaling (MDS) was used to evaluate the effects of forest cover on the composition of mosquito populations at different radii (100-, 250-, and 1,000-m-radius buffer areas). The MDS provided 2 dimensions with values that indicated a higher similarity in the composition of culicid populations between sites 1 and 3, while site 2 was separate from the others in the ordination space. Site 2 had a much higher forest cover ratio at 100-m radius compared with sites 1 and 3. We found a possible relationship between the forest cover and the composition of the mosquito populations only in the 100-m radius. These results enabled us to infer that RH directly favored the activity of mosquito populations and that the forest cover located closest to the sampling site may influence the species composition. Since mosquito abundance was higher in the sites with lower local forest cover, forest fragmentation may be a key factor on the presence of WYF vector.

Larvicidal study of tetrahydropyrimidine scaffolds against Anopheles arabiensis and structural insight by single crystal X-ray studies.

A series of methyl or ethyl 4-(substitutedphenyl/pyridyl)-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (HPM) analogues 4a-g were synthesized and evaluated for larvicidal activity against Anopheles arabiensis. These newly synthesized compounds were characterized by spectral studies such as FT-IR, NMR (1 H and 13 C), LC-MS, and elemental analysis. The conformational features and supramolecular assembly of molecules 4a, 4b, and 4e were further analyzed from single crystal X-ray study. The larvicidal activity of these tetrahydropyrimidine pharmacophore series was analyzed based on their relative substituents. Among the synthesized HPM analogous from the series, compounds 4d and 4e both having electron withdrawing chlorine group on phenyl ring at the fourth position of the tetrahydropyrimidine pharmacophore exhibited the most promising larvicidal activity.