WE report that mefloquine (2,8-bis-(trifluoromethyl)-α-(2-pipe-ridyl)-4-quinolinemethanol1, see Fig. 1) clinically useful against drug-resistant Plasmodium falciparum malaria (G. M. Trenholme, unpublished), does not significantly bind to calf thymus DNA. This constitutes the first reported case of an active compound in the quinoline–acridine class of antimalarials which does not strongly bind to DNA by intercalation.

Mefloquine, a clinically useful quinolinemethanol antimalarial which does not significantly bind to DNA.

Introduction: Antimalarial drugs are essential weapons to fight malaria and have been used effectively since the 17th century. However, P.falciparum resistance has been reported to almost all available antimalarial drugs, including artemisinin derivatives, raising concerns that this could jeopardize malaria elimination.Areas covered: In this article, we present a historical perspective of antimalarial drug resistance, review current evidence of resistance to available antimalarial drugs and discuss possible mitigating strategies to address this challenge.Expert commentary: The historical approach to drug resistance has been to change the national treatment policy to an alternative treatment. However, alternatives to artemisinin-based combination treatment are currently extremely limited. Innovative approaches utilizing available schizonticidal drugs such as triple combination therapies or multiple first line treatments could delay the emergence and spread of drug resistance. Transmission blocking ...

Malaria medicines to address drug resistance and support malaria elimination efforts.

The naturally fluorescent compound quinine has long been used to treat malaria infections. Although some evidence suggests that quinine acts in the parasite food vacuole, the mechanism of action of quinine has not yet been resolved. The Plasmodium falciparum multidrug resistance (pfmdr1) gene encodes a food vacuolar membrane transporter and has been linked with parasite resistance to quinine. The effect of multiple pfmdr1 copies on the subcellular localization of quinine was explored. Fluorescence microscopy was used to evaluate the subcellular localization of quinine in parasites containing different pfmdr1 copy numbers to determine if copy number of the gene affects drug localization. The acidotropic dye LysoTracker Red was used to label the parasite food vacuole. Time-lapse images were taken to determine quinine localization over time following quinine exposure. Regardless of pfmdr1 copy number, quinine overlapped with haemozoin but did not colocalize with LysoTracker Red, which labeled the acidic parasite food vacuole. Quinine localizes to a non-acidic compartment within the food vacuole possibly haemozoin. Pfmdr1 copy number does not affect quinine subcellular localization.

https://cdr.lib.unc.edu/downloads/rn301358k

Quinine localizes to a non-acidic compartment within the food vacuole of the malaria parasite Plasmodium falciparum

Background Malaria is among the leading causes of mortality and morbidity. Moreover, the emergence of resistance to antimalarial drugs is a major problem in controlling the disease. This makes the development of novel antimalarial drugs a necessity. Medicinal plants are important sources in discovering antimalarial drugs. Schinus molle is claimed for its antimalarial effect in Ethiopian folkloric medicine and endowed with in vitro antiplasmodial activity. In the present study, the in vivo antimalarial activity of the plant was investigated. Methods Acute toxicity was carried out using a standard procedure. To screen the in vivo antimalarial activity of the plant was investigated. S. molle against Plasmodium berghei (ANKA), a 4-day suppressive test was employed. The extracts and fractions were given to infected mice by oral gavage at 100, 200, and 400 mg/kg/day for four consecutive days. Parameters such as parasitemia were then evaluated. Results Any sign of toxicity was not observed in the oral acute toxicity test. The crude extracts and solvent fractions exerted a significant (p < 0.05) inhibition of parasite load compared to the negative control. The highest inhibition (66.91%) was exhibited by the 400 mg/kg/day dose of 80% methanolic crude extract. Among the fractions, chloroform fraction demonstrated maximal chemosuppressive effect (55.60%). Moreover, crude extracts and solvent fractions prevented body weight loss, reduction in temperature, and anemia compared to the negative control. Except the aqueous fraction, the tested plant extracts were able to significantly prolong the survival time of infected mice. Conclusion The findings of the present study confirmed the safety and a promising in vivo antimalarial activity of S. molle, thus supporting the traditional claim and in vitro efficacy. In-depth investigations on the plant, however, are highly recommended.in vivo antimalarial activity of the plant was investigated. S. molle against in vitro antiplasmodial activity. In the present study, the.

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Antimalarial Activity of Aqueous and 80% Methanol Crude Seed Extracts and Solvent Fractions of Schinus molle Linnaeus (Anacardiaceae) in Plasmodium berghei-Infected Mice

The object of the present paper is to study of radius of convexity two certain integral operators as follows \begin{equation*} 
F(z):=\int_{0}^{z}\prod_{i=1}^{n}\left(f'_i(t)\right)^{\gamma_i}{\rm d}t \end{equation*} and \begin{equation*} 
J(z):=\int_{0}^{z}\prod_{i=1}^{n}\left(f'_i(t)\right)^{\gamma_i}\prod_{j=1}^{m} 
\left(\frac{g_j(z)}{z}\right)^{\lambda_j}{\rm d}t, \end{equation*} where $\gamma_i, \lambda_i\in\mathbb{C}$, $f_i$ $(1\leq i\leq n)$ and $g_j$ $(1\leq j\leq m)$ belong to the certain subclass of analytic functions.

/pdf/radii-of-convexity-of-integral-operators-56n3qosxrf.pdf

Radii of convexity of integral operators

New antimalarial drugs are required, partly because of the emergence of drug resistant strains of malaria parasites and partly because better compounds are needed to cure relapsing tertian malaria. In reviewing the diverse modes of action of currently used anti-malarials, against a background of the pathogenesis of malaria, attention is drawn to deficiencies in our knowledge. Even less do we understand how the malaria parasite becomes resistant to certain drugs, in particular chloroquine. New approaches to the problem include the application of combinations of existing antimalarials, and the search for new drugs on an unprecedentedly vast scale. Out of over a quarter million compounds that have recently been screened, a handful are now in clinical trial and are showing great promise for the treatment of multiple resistant falciparum malaria. The paper concludes by summarizing current recommendations for the prophylaxis and therapy of malaria due to drug resistant parasites.

https://pmj.bmj.com/content/postgradmedj/49/574/573.full.pdf

W. Peters

Papers

Antimalarial drugs and their actions