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An Introduction to the Ethnopharmacology of Wild Plants
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Shandesh Bhattarai, Christiane Mendes Feitosa, Mahendra Rai
The Combretastatins are a family of stilbenes that act as anti-angiogenic agents resulting in tumor necrosis (Cragg et al. 2002). Combretastatins isolated from the bark of Combretum caffrum showed to be active against colon, lung and leukemia cancers (Petit et al. 1987, Ohsumi et al. 1998). Homoharringtonine isolated from the Cephalotaxus harringtonia is at present in clinical use (Itokawa et al. 2005). Betulinic acid, primarily from Betula species (Cichewitz and Kouzi 2004), but also isolated from Zizyphus mauritiana, Z. rugosa and Z. oenoplia displayed selective cytotoxicity against human melanoma cell lines. Silvestrol from the fruits of Aglaila sylvestre, exhibited cytotoxicity against lung and breast cancer cell lines (Pisha et al. 1995). Other plant derived agents in clinical use are homoharringtonine isolated from Cephalotaxus harringtonia and elliptinium isolated from species of several genera of the Apocynaceae including Bleekeria vitensis, with reputed anti-cancer properties. Several Terminalia species have reportedly been used in the treatment of cancer.
Diagnostic and management strategies for chronic hepatitis E infection
Published in Expert Review of Anti-infective Therapy, 2023
Florence Abravanel, Sébastien Lhomme, Olivier Marion, Jean Marie Péron, Nassim Kamar, Jacques Izopet
There is clearly a need to develop effective direct-acting antivirals for HEV and/or to repurpose old drugs with anti-HEV activity. However, the pharmaceutical industry does not seem to be interested in developing anti-HEV drugs. Direct active agents with high antiviral activity and low side effect against HEV should be developed as it was for the treatment of chronic hepatitis C. Several in vitro or in vivo models can be used to study HEV replication and are suitable for antiviral drug testing. Cells line or organoids can support the replication of HEV [68,69]. Cynomolgus monkeys or pigs treated with immunosuppressive drugs can reproduce the chronic hepatitis E observed in humans [70,71]. But these large animal models are difficult to use. Human liver chimeric mouse models based on immunodeficient mice repopulated with human hepatocytes have been shown to support persistent infection of genotype 1 and 3 HEV [72]. A large panel of compounds have been identified as a potential new antiviral agent against HEV. Old drugs such as nucleos(t)ide analogs [73], ivermectin [74], azithromycin [75], gemcitabine [76] inhibit HEV in vitro. Drug screening in organoids identified brequinar and homoharringtonine as potent HEV inhibitors, which are also effective against variants harboring the G1634R mutation [69]. The natural compound silvestrol inhibits HEV replication in vitro and in vivo with additive effect to RBV [77,78]. All these compounds have to be evaluated in clinical trials in the fragile population of immunosuppressed patients.
Emerging drug targets for triple-negative breast cancer: a guided tour of the preclinical landscape
Published in Expert Opinion on Therapeutic Targets, 2022
Xuemei Xie, Jangsoon Lee, Toshiaki Iwase, Megumi Kai, Naoto T Ueno
Eukaryotic translation initiation factor 4A-1 (eIF4A1) is a component of the eukaryotic translation initiation eIF4F complex, which plays a pivotal role in cancer development by integrating mitogenic signals to amplify the production of oncogenic proteins [140]. As an mRNA helicase, eIF4A1 unwinds oncogenic mRNAs to permit their translation; these oncogenic mRNAs include BIRC5 (survivin), MDM2, MCL1, BCL2, ROCK1, SIN1, CCND1, and CCND3 [141,142], which are implicated in the survival and metastasis of breast CSCs and bulk tumor cells [143]. Because eIF4A1 supports the cancer proteome to enable tumor progression and metastasis, several small-molecule inhibitors have been developed to disrupt eIF4A1ʹs activity, including pateamine A, hippuristanol, silvestrol, cardiac glycosides, and rocaglates. These inhibitors demonstrated remarkable anti-tumor efficacy in TNBC preclinical models [143,144]. New amidino-rocaglate derivatives have recently been developed. For instance, rocaglamide A reduced eIF4A1-mediated stemness in TNBC [143]. The selective eIF4A1 inhibitor eFT226 (Zotatifin) is being evaluated in phase I clinical trials for patients with advanced solid tumors (NCT04092673). Overall, findings to date indicate that eIF4A1 is a therapeutic target for TNBC.
An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery
Published in Expert Opinion on Drug Discovery, 2023
There have not been many studies conducted to establish the antiviral properties of substances obtained from plants against MERS-CoV infection. In vitro investigation reported that silvestrol, a phytochemical extracted from Aglaia sp., greatly suppressed MERS-CoV replication [127]. In CoV-infected human embryonic lung fibroblast (MRC-5) cells, silvestrol acted as a strong inhibitor of cap-dependent viral mRNA translation. The EC50 values for silvestrol against MERS-CoV and HCoV-229E were 1.3 and 3 nM, respectively.