Present-day anthelmintics and perspectives on future new targets

Abstract

In absence of vaccines for the majority of helminths, chemotherapy is still the mainstay for controlling human helminthiases. However, a limited number of drugs are available in the market to combat parasitic helminths in human. Besides, the development and spread of drug resistance have declined the use of most currently available anthelmintics. Clearly, availability of new anthelmintic agents will be essential in the next few years. More research into the mechanisms of drug actions and their targets are eminent for the discovery and development of novel anthelmintic agents. Recent drug discovery techniques mostly rely on mechanism-based screening of compounds on heterologously expressed targets in bacterial, mammalian or yeast cells. Although this is usually a successful approach, it is money- and time-consuming; meanwhile, pharmaceutical companies prefer the tested target that is chosen based on basic research. The nervous system is the site of action of several chemotherapeutics including pesticides and antinematode drugs; accordingly, the nervous system continues to be a promising target. Recent advances in exploring helminths' nervous system, neurotransmitters and receptors have paved the way for the development of potential agents targeting the nervous system and its components.

Pharmacological profile of Ascaris suum ACR‐16, a new homomeric nicotinic acetylcholine receptor widely distributed in Ascaris tissues

“…No current vaccine against nematode parasite infections of humans is effective (Hewitson and Maizels, ), so control of these infections relies on chemotherapy. Regrettably, there are a limited number of classes of anthelmintics (Martin, ; Kaminsky et al , ), which, with the repeated large scale use of the drugs, has led to the development of resistance in animals (Wolstenholme et al , ), and concerns about the development of resistance in humans (Taman and Azab, ). The increasing resistance means that novel drug targets are required to overcome this resistance.…”

Beautyberry (Callicarpa arborea) as an Antiparasitic Agent Against Raillietina echinobothrida, an Intestinal Tapeworm

“…Thus, their effects are most directly noted as structural damages in these organs. 23,24 The only areas of the tegument not entirely covered by microtriches are the rims of suckers (spines) and rostellum (hooks) on the head part, the scolex. These spines and hooks are special parasitic adaptations for anchoring on the tissue surfaces, such as intestinal lumen, of the hosts.…”

Microfluidic platform for electrophysiological recordings from host-stage hookworm and Ascaris suum larvae: A new tool for anthelmintic research

“…Many current anthelmintic drugs act on proteins involved in electrical signaling—neurotransmitter receptors and ion channels—and these molecules remain valuable targets for anthelmintic drug development (Wolstenholme, 2011, Taman and Azab, 2014). Therefore, a screening method that reads out electrophysiological function could help prioritize and characterize hits when seeking new anthelmintics, and provide more mechanistic insight than nonspecific phenotypes such as death.…”