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      Bioactive Natural Spirolactone-Type 6,7- seco- ent-Kaurane Diterpenoids and Synthetic Derivatives

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          Abstract

          Diterpenoids are widely distributed natural products and have caused considerable interest because of their unique skeletons and antibacterial and antitumor activities and so on. In light of recent discoveries, ent-kaurane diterpenoids, which exhibit a wide variety of biological activities, such as anticancer and anti-inflammatory activities, pose enormous potential to serve as a promising candidate for drug development. Among them, spirolactone-type 6,7- seco- ent-kaurane diterpenoids, with interesting molecular skeleton, complex oxidation patterns, and bond formation, exhibit attractive activities. Furthermore, spirolactone-type diterpenoids have many modifiable sites, which allows for linking to various substituents, suitable for further medicinal study. Hence, some structurally modified derivatives with improved cytotoxicity activities are also achieved. In this review, natural bioactive spirolactone-type diterpenoids and their synthetic derivatives were summarized.

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          Most cited references85

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          Counting on natural products for drug design.

          Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.
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            Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer

            Paclitaxel, a class of taxane with microtubule stabilising ability, has remained with platinum based therapy, the standard care for primary ovarian cancer management. A deeper understanding of the immunological basis and other potential mechanisms of action together with new dosing schedules and/or routes of administration may potentiate its clinical benefit. Newer forms of taxanes, with better safety profiles and higher intratumoural cytotoxicity, have yet to demonstrate clinical superiority over the parent compound.
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              Diterpenoids from Isodon species and their biological activities.

              Isodon species (Labiatae) are widely distributed plants, many of which are used in folk medicine. Over the past twenty years, they have received considerable phytochemical and biological attention. Thestructures of their many diterpenoids constituents, especially those with an ent-kaurane skeleton, have been elucidated. The significant phytochemical and pharmacological diterpenoids form the subject of this review. There are 290 references.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                08 November 2018
                November 2018
                : 23
                : 11
                : 2914
                Affiliations
                [1 ]Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China; lihaonan073@ 123456163.com (H.L.); jiaorunwei@ 123456163.com (R.J.); 13130821899@ 123456sina.cn (J.M.); lzl1030@ 123456hotmail.com (Z.L.); huimhua@ 123456163.com (H.H.)
                [2 ]Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; cpuxst@ 123456163.com (S.X.); jinyixu@ 123456china.com (J.X.)
                [3 ]Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222001, China; lixu19900611@ 123456163.com
                [4 ]School of Public Health, Qingdao University, Qingdao 266021, China; xianhuawang126@ 123456sina.com
                Author notes
                [* ]Correspondence: lidahong0203@ 123456163.com ; Tel.: +86-24-2398-6465
                Author information
                https://orcid.org/0000-0002-6964-4619
                Article
                molecules-23-02914
                10.3390/molecules23112914
                6278314
                30413071
                a733bbb2-8db0-40eb-9f5b-a5afece9d863
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 October 2018
                : 05 November 2018
                Categories
                Review

                spirolactone-type,6,7-seco-ent-kaurane,diterpenoid,natural product,synthetic derivative

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