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  3. Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design

Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design

  • Bioorg Med Chem Lett. 2020 Aug 15;30(16):127349. doi: 10.1016/j.bmcl.2020.127349.
Fernanda S de Sousa 1,  João L Baldim 2,  Ricardo A Azevedo 3,  Carlos R Figueiredo 4,  Pauline Pieper 5,  Claire E Sear 5,  Edward A Anderson 5,  João Henrique G Lago 6
Affiliations

Affiliations

  • 1 Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of São Paulo, São Paulo 09972-270, Brazil.
  • 2 Center of Natural and Human Sciences, Federal University of ABC, Santo André 09210-580, Brazil; Federal Institute of Education, Science and Technology of South of Minas Gerais - IFSULDEMINAS, Minas Gerais 37890-000, Brazil.
  • 3 Department of Immunology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77054, USA.
  • 4 Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo 04021-001, Brazil.
  • 5 Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK.
  • 6 Center of Natural and Human Sciences, Federal University of ABC, Santo André 09210-580, Brazil. Electronic address: [email protected].
PMID: 32631547 DOI: 10.1016/j.bmcl.2020.127349
Abstract

Dehydrodieugenol B and five related natural neolignans were isolated from the Brazilian plant species Nectandra leucantha. Three of these compounds were shown to be active against murine (B16F10) and human (A2058) melanoma cells but non-toxic to human fibroblasts (T75). These results stimulated the preparation of a series of 23 semi-synthetic derivatives in order to explore structure-activity relationships and study the biological potential of these derivatives against B16F10 and A2058 cell lines. These structurally-related neolignan derivatives were analyzed by multivariate statistics and machine learning, which indicated that the most important characteristics were related to their three-dimensional structure and, mainly, to the substituents on the neolignan skeleton. The results suggested that the presence of hydroxyl or alkoxyl groups at positions 3, 4 and 5 (with appropriate sidechains) promoted an increase in electropological and charge density, which seem to be important for biological activity against murine (B16F10) and human (A2058) melanoma cells.

Keywords

A2058; B16F10; Cytotoxic; Multivariate analysis; Neolignans; Semi-synthetic derivatives.

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