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      An overview on natural farnesyltransferase inhibitors for efficient cancer therapy

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          Abstract

          As one of the world’s five terminally ills, tumours can cause important genetic dysfunction. However, some current medicines for tumours usually have strong toxic side effects and are prone to drug resistance. Studies have found that farnesyltransferase inhibitors (FTIs) extracted from natural materials have a good inhibiting ability on tumours with fewer side effects. This article describes several FTIs extracted from natural materials and clarifies the current research progress, which provides a new choice for the treatment of tumours.

          Executive summary

          Farnesyltransferase (FTase)

          • When Ras gene is activated, it becomes an oncogene with oncogenic activity. Ras protein plays a crucial role in cancer cells. FTase is the first step to activate Ras protein.

          • FTIs not only have anti-tumour effects, but also makes great contribution to the treatment of plasmodium falciparum, parasitic diseases and progeria.

          • There are still some problems with FTIs, but natural products FTIs are worthy of further research as a new class of low-toxic, safe and effective anticancer drugs. Summarised natural product-derived FTase inhibitors

          • This review summarised several FTIs extracted from natural materials and clarifies their anti-tumour activity (IC 50 value) and structure, providing a reference for further research on tumour therapy.

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          Most cited references124

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          Biology and biotechnology of Trichoderma

          Fungi of the genus Trichoderma are soilborne, green-spored ascomycetes that can be found all over the world. They have been studied with respect to various characteristics and applications and are known as successful colonizers of their habitats, efficiently fighting their competitors. Once established, they launch their potent degradative machinery for decomposition of the often heterogeneous substrate at hand. Therefore, distribution and phylogeny, defense mechanisms, beneficial as well as deleterious interaction with hosts, enzyme production and secretion, sexual development, and response to environmental conditions such as nutrients and light have been studied in great detail with many species of this genus, thus rendering Trichoderma one of the best studied fungi with the genome of three species currently available. Efficient biocontrol strains of the genus are being developed as promising biological fungicides, and their weaponry for this function also includes secondary metabolites with potential applications as novel antibiotics. The cellulases produced by Trichoderma reesei, the biotechnological workhorse of the genus, are important industrial products, especially with respect to production of second generation biofuels from cellulosic waste. Genetic engineering not only led to significant improvements in industrial processes but also to intriguing insights into the biology of these fungi and is now complemented by the availability of a sexual cycle in T. reesei/Hypocrea jecorina, which significantly facilitates both industrial and basic research. This review aims to give a broad overview on the qualities and versatility of the best studied Trichoderma species and to highlight intriguing findings as well as promising applications.
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            Acute, sublethal, antifeedant, and synergistic effects of monoterpenoid essential oil compounds on the tobacco cutworm, Spodoptera litura (Lep., Noctuidae).

            Monoterpenoids (terpenes and biogenically related phenols) commonly found in plant essential oils were tested for acute toxicity via topical application to tobacco cutworms (Spodoptera litura Fab.). The most toxic among 10 such compounds was thymol (LD(50) = 25.4 microg/larva) from garden thyme, Thymus vulgaris. The compounds were then tested for sublethal effects, specifically inhibition of larval growth after topical application of low doses. Among 6 compounds tested, an LD(10) dose reduced growth by 20% on average 3 days after administration. Feeding deterrence was determined using a cabbage leaf disk choice test. The most deterrent compound was thymol, with a DC(50) of 85.6 microg/cm(2) leaf disk area. Because minor constituents in complex essential oils have been suggested to act as synergists, binary mixtures of the compounds were tested for synergy vis à vis acute toxicity and feeding deterrence. trans-Anethole acted synergistically with thymol, citronellal, and alpha-terpineol, in terms of both acute toxicity and feeding deterrence. On the basis of these findings, several complex mixtures were developed and tested as leads for effective control agents. Candidate mixtures demonstrated good synergistic effects. The observed LD(50) of mixture 3 was 40.6 microg/larvae compared to an expected value of 74.6 microg/larvae. The result of this research is a proprietary product suitable for commercial production.
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              Biological activities of sesquiterpene lactones

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                Author and article information

                Journal
                J Enzyme Inhib Med Chem
                J Enzyme Inhib Med Chem
                IENZ
                ienz20
                Journal of Enzyme Inhibition and Medicinal Chemistry
                Taylor & Francis
                1475-6366
                1475-6374
                2020
                20 April 2020
                : 35
                : 1
                : 1027-1044
                Affiliations
                School of Life Science, Ludong University , Yantai, Shandong, China
                Author notes

                #Both authors contributed equally to this work.

                CONTACT Gao Hongwei gaohongw369@ 123456163.com School of Life Science, Ludong University , Yantai, Shandong, 264025, China
                Article
                1732366
                10.1080/14756366.2020.1732366
                7191900
                32308053
                30ed7eb4-09e0-4fe2-bcc7-6116d240f00b
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 August 2019
                : 11 January 2020
                : 09 February 2020
                Page count
                Figures: 9, Tables: 4, Pages: 18, Words: 10274
                Funding
                Funded by: Natural Science Foundation of Shandong, China
                Award ID: ZR201808030032
                Funded by: High-end Talent Team Construction Foundation of Ludong University
                Award ID: 108-10000318
                Funded by: Science and Technology Innovation Development Plan Foundation of Yantai, China
                Award ID: 2020YT06000628
                Award ID: 2019HX119
                This work was financially supported by Natural Science Foundation of Shandong, China [Grant No. ZR2019MC004]. This work was also financially supported by the high-end talent team construction foundation [Grant No. 108-10000318].
                Categories
                Review Article

                Pharmaceutical chemistry
                tumour,ftis,ras protein,natural materials,inhibitors
                Pharmaceutical chemistry
                tumour, ftis, ras protein, natural materials, inhibitors

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