Malaria remains a serious worldwide health danger and massive economic trouble to disease-endemic nations. Presently, 250 million of malarial cases are expected worldwide. The emergence of fighting of the Plasmodium parasite against the first-line antimalarial drugs has fueled research attention in the way of designing new scaffolds as well as strategies to counter the drug resistance. Chalcones are simple and well-known analogs, which were found in a huge number of natural compounds and also been prepared according to their suitable synthetic approaches. This review illustrates the current progresses on structure-activity relationship (SAR) and mechanism of diverse types of chalcone derivatives that play a significant role for the development of novel safe, less toxic and highly active antimalarials. This present mini-review will be useful to scientists in research fields of medicinal chemistry, organic synthesis, and also various biological applications particularly for the development of novel antiplasmodial and antimalarial agents.

The malaria parasite resistance to the existing drugs is a serious problem to the currently used antimalarials and, thus, highlights the urgent need to develop new and effective anti-malarial molecules. This could be achieved either by the identification of the new drugs for the validated targets or by further refining/improving the existing antimalarials; or by combining previously effective agents with new/existing drugs to have a synergistic effect that counters parasite resistance; or by identifying novel targets for the malarial chemotherapy. In this review article, a comprehensive collection of some of the novel molecular targets has been enlisted for the antimalarial drugs. The targets which could be deliberated for developing new anti-malarial drugs could be: membrane biosynthesis, mitochondrial system, apicoplasts, parasite transporters, shikimate pathway, hematin crystals, parasite proteases, glycolysis, isoprenoid synthesis, cell cycle control/cycline dependent kinase, redox system, nucleic acid metabolism, methionine cycle and the polyamines, folate metabolism, the helicases, erythrocyte G-protein, and farnesyl transferases. Modern genomic tools approaches such as structural biology and combinatorial chemistry, novel targets could be identified followed by drug development for drug resistant strains providing wide ranges of novel targets in the development of new therapy. The new approaches and targets mentioned in the manuscript provide a basis for the development of new unique strategies for antimalarial therapy with limited off-target effects in the near future.

The gastrointestinal nematodes (GIN) stand out as an important cause of disease in small ruminant, especially on goat farm. Widespread resistance to synthetic anthelminthics has stimulated the research for alternative strategies of parasite control, including the use of medicinal plants. The present work summarizes the in vitro and in vivo studies of plants with activity against GIN of goats, focusing on the description of chemical constituents related to this effect. This review retrieved 56 scientific articles from 2008 to 2018 describing more than 100 different plant species. The most frequently investigated family was Fabaceae (30.7%). Most in vitro studies on the activity of plant extracts and fractions were carried out with of free-living stages nematodes. In vivo studies were conducted mainly with the use of plants in animal feed and generally showed lower effectiveness compared to in vitro assays. The main plant secondary metabolites associated with anthelmintic effect are condensed tannins, saponin and flavonoids. However, the studies with compounds isolated from plants and elucidation of their mechanisms of action are scarce. Herbal medicines are thought to be promising sources for the development of effective anthelmintic agents.

Malaria represents a significant health issue, and novel effective drugs are needed to address parasite resistance that has emerged to the current drug arsenal. The most popular antimalarial drugs are focused on the 7-chloro-4-aminoquinoline [e.g., chloroquine (CQ), amodiaquine (AQ), isoquine (IQ), and tebuquine (TBQ)], artemisinin, and atovaquone systems. Recently, endochin has been used as a platform to design a variety of novel potent and safe antimalarial agents named endochin-like quinolones (ELQs). Also, antimalarial quinolones have been constructed from other quinolones drugs such as ICI-56780 and floxacrine. Trifluoromethyl substitution has provided a significant increase in the antimalarial response of many of the designed ELQs against Plasmodium-resistant strains and for in vivo models. In particular, attachment of a substituted trifluoromethoxy (or trifluoromethyl in some cases) biaryl side chain at 2-, 3-, 4-, or 6-position of the quinolone core has shown to be crucially important to generate selective and potent novel ELQs. Furthermore, 6-chloro and 7-methoxy moieties on the quinolone core have been identified as essential pharmacophores when the trifluoromethoxy biaryl side chain is placed at 2- or 3-position of the quinolone core. Methyl or ethyl ester attached at 3-position is essential when the trifluoromethoxy aryl side chain is attached at 6- or 7-position of the quinolone core. Some promising ELQs are currently under clinical trials, representing an excellent platform for the design of new potent, selective, effective, and safe antimalarial drugs against emergent resistance malarial models.

Leishmaniasis is a neglected disease caused by protozoan belonging to the Leishmania genus. There are at least 16 pathogenic species for humans that are able to cause different clinical forms, such as cutaneous or visceral leishmaniasis. In spite of the different species and clinical forms, the treatment is performed with few drug options that, in most cases, are considered outdated. In addition, patients under classical treatment show serious side effects during drug administration, moreover parasites are able to become resistant to medicines. Thus, it is believed and well accepted that is urgent and necessary to develop new therapeutic options to overpass these concerns about conventional therapy of leishmaniasis. The present review will focus on the efficacy, side effects and action mechanism of classic drugs used in the treatment of leishmaniasis, as well as the importance of traditional knowledge for directing a rational search toward the discovery and characterization of new and effective molecules (in vivo assays) from plants to be used against leishmaniasis.

One of the main problems of Chagas disease (CD), the parasitic infection caused by Trypanosoma cruzi, is the lack of a completely satisfactory treatment, which is currently based on two old nitroheterocyclic drugs (i.e., nifurtimox and benznidazole) that show important limitations for treating patients. In this context, many laboratories look for alternative therapies potentially applicable to the treatment, and therefore, research in CD chemotherapy works in the design of experimental protocols for detecting molecules with activity against T. cruzi. Phenotypic assays are considered the most valuable strategy for screening these antiparasitic compounds. Among them, in vitro experiments are the first step to test potential anti-T. cruzi drugs directly on the different parasite forms (i.e., epimastigotes, trypomastigotes, and amastigotes) and to detect cytotoxicity. Once the putative trypanocidal drug has been identified in vitro, it must be moved to in vivo models of T. cruzi infection, to explore (i) acute toxicity, (ii) efficacy during the acute infection, and (iii) efficacy in the chronic disease. Moreover, in silico approaches for predicting activity have emerged as a supporting tool for drug screening procedures. Accordingly, this work reviews those in vitro, in vivo, and in silico methods that have been routinely applied during the last decades, aiming to discover trypanocidal compounds that contribute to developing more effective CD treatments.

Leishmaniasis is a group of infectious neglected tropical diseases caused by more than 20 pathogenic species of Leishmania sp. Due to the limitations of the current treatments available, chalcone moiety has been drawn with a lot of attention due to the simple chemistry and synthesis, being reported with antileishmanial activity in particular against amastigote form. This review aims to provide an overview towards antileishmanial activity of chalcones derivatives against amastigote form for Leishmania major, L. amazonensis, L. panamensis, L. donovani and L. infantum as well as their structure-activity relationship (SAR), molecular targets and in silico ADMET evaluation. In this way, it is expected that this review may support the research and development of new promising chalcones candidates a leishmanicidal drugs.

Trichomonas vaginalis is a major non-viral sexually-transmitted infection resulted into serious obstetrical and gynecological troubles. The increasing resistance to nitroimidazole therapy and recurrence makes it crucial to develop new drugs against trichomoniasis. Over the past few years, a large number of research articles highlighting the synthetic and natural product research to combat Trichomonas vaginalis have been published. Electronic databases were searched to collect all data from the year 2006 through June 2017 for anti-Trichomonas activity potential of synthetic and natural products. This review article put together the synthetic and natural product research to find out an effective metronidazole alternative to cure trichomoniasis.

The emergence of resistance to former first-line antimalarial drugs has been an unmitigated disaster. In recent years, artemisinin class drugs have become standard and they are considered an essential tool for helping to eradicate the disease. However, their ability to reduce morbidity and mortality and to slow transmission requires the maintenance of effectiveness. Recently, an artemisinin delayed-clearance phenotype was described. This is believed to be the precursor to resistance and threatens local elimination and global eradication plans. Understanding how resistance emerges and spreads is important for developing strategies to contain its spread. Resistance is the result of two processes: (i) drug selection of resistant parasites; and (ii) the spread of resistance. In this review, we examine the factors that lead to both drug selection and the spread of resistance. We then examine strategies for controlling the spread of resistance, pointing out the complexities and deficiencies in predicting how resistance will spread.

Malaria remains a major world health problem following the emergence and spread of Plasmodium falciparum that is resistant to the majority of antimalarial drugs. This problem has since been aggravated by a decreased sensitivity of Plasmodium vivax to chloroquine. This review discusses strategies for evaluating the antimalarial activity of new compounds in vitro and in animal models ranging from conventional tests to the latest high-throughput screening technologies. Antimalarial discovery approaches include the following: the discovery of antimalarials from natural sources, chemical modifications of existing antimalarials, the development of hybrid compounds, testing of commercially available drugs that have been approved for human use for other diseases and molecular modelling using virtual screening technology and docking. Using these approaches, thousands of new drugs with known molecular specificity and active against P. falciparum have been selected. The inhibition of haemozoin formation in vitro, an indirect test that does not require P. falciparum cultures, has been described and this test is believed to improve antimalarial drug discovery. Clinical trials conducted with new funds from international agencies and the participation of several industries committed to the eradication of malaria should accelerate the discovery of drugs that are as effective as artemisinin derivatives, thus providing new hope for the control of malaria.