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      Review of bioactive secondary metabolites from marine bryozoans in the progress of new drugs discovery

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          Abstract

          <p class="first" id="d723319e213">Marine bryozoans play an important role for the discovery of novel bioactive compounds among marine organisms. In this review, we summarize 164 new secondary metabolites including macrocyclic lactones, sterols, alkaloids, sphingolipids and so forth from 24 marine bryozoans in the last two decades. The structural features, bioactivity, structure–activity relationship, mechanism and strategies to address the resupply of these scarce secondary metabolites are discussed. The structural and bioactive diversity of the secondary metabolites from marine bryozoans indicated the possibility of using these compounds, especially bryostatin 1 ( <b>1</b>), bryostatin analog ( <b>BA1</b>), alkaloids ( <b>50</b>, <b>53, 127–128</b> and <b>134–139</b>), sphingolipids sulfates ( <b>148</b> and <b>149</b>) and sulfur-containing aromatic compound ( <b>160</b>), as the starting points for new drug discovery. </p>

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          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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            Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy.

            The protein kinase C (PKC) agonist bryostatin-1 has shown significant ex-vivo potency to revert HIV-1 latency, compared with other latency reversing agents (LRA). The safety of this candidate LRA remains to be proven in treated HIV-1-infected patients.
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              The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma.

              Progress has been made recently in developing antibody-drug conjugates (ADCs) that can selectively deliver cancer drugs to tumor cells. In principle, the idea is simple: by attaching drugs to tumor-seeking antibodies, target cells will be killed and nontarget cells will be spared. In practice, many parameters needed to be addressed to develop safe and effective ADCs, including the expression profiles of tumor versus normal tissues, the potency of the drug, the linker attaching the drug and placement of the drug on the antibody, and the pharmacokinetic and stability profiles of the resulting ADC. All these issues had been taken into account in developing brentuximab vedotin (Adcetris), an ADC that recently received accelerated approval by the US Food and Drug Administration for the treatment of relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL). Research is under way to extend the applications of brentuximab vedotin and to advance the field by developing other ADCs with new linker and conjugation strategies.
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                Author and article information

                Journal
                Future Medicinal Chemistry
                Future Medicinal Chemistry
                Future Science Ltd
                1756-8919
                1756-8927
                June 2018
                June 2018
                : 10
                : 12
                : 1497-1514
                Affiliations
                [1 ]Research &amp; Development Center of Biorational Pesticide, College of Plant Protection, Northwest A&amp;F University, Yangling 712100, PR China
                [2 ]Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, PR China
                [3 ]Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702–21201, USA
                Article
                10.4155/fmc-2018-0012
                6040070
                29788787
                d0d4778c-8417-4e6a-a78e-3e82ca788db6
                © 2018
                History

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