Abstract
Plants have been used for centuries to treat several illnesses. The Plectranthus genus has a vast variety of species that has allowed the isolation of cytotoxic compounds with notable activities. The abietane diterpenes 6,7-dehydroroyleanone (DeRoy, 1), 7α-acetoxy-6β-hydroxyroyleanone (Roy, 2), and Parvifloron D (ParvD, 3) were obtained from Plectranthus spp. and showed promising biological activities, such as cytotoxicity. The inhibitory effects of the different natural abietanes (1-3) were compared in MFC7, SkBr3, and SUM159 cell lines, as well as SUM159 grown in cancer stem cell-inducing conditions. Based on the royleanones’ bioactivity, the derivatives RoyBz (4), RoyBzCl (5), RoyPr2 (6), and DihydroxyRoy (7), previously obtained from 2, were selected for further studies. Protein kinases C (PKCs) are involved in several carcinogenic processes. Thus, PKCs are potential targets for cancer therapy. To date, the portfolio of available PKC modulators remains very limited due to the difficulty of designing isozyme-selective PKC modulators. As such, molecular docking was used to evaluate royleanones 1-6 as predicted isozyme-selective PKC binders. Subtle changes in the binding site of each PKC isoform change the predicted interaction profiles of the ligands. Subtle changes in royleanone substitution patterns, such as a double substitution only with non-substituted phenyls, or hydroxybenzoate at position four that flips the binding mode of ParvD (3), can increase the predicted interactions in certain PKC subtypes.
Highlights
IntroductionMany commercially available chemotherapeutic agents are plant-derived products commercially available chemotherapeutic agents are (e.g., paclitaxel,many vincristine, irinotecan), some may induce resistance andplant-derived toxic effects products that can (e.g., paclitaxel, vincristine, irinotecan), some may induce resistance and toxic effects thatnovel can compromise therapy success and consequent patient recovery [1]
Many commercially available chemotherapeutic agents are plant-derived products commercially available chemotherapeutic agents are, some may induce resistance andplant-derived toxic effects products that can, some may induce resistance and toxic effects thatnovel can compromise therapy success and consequent patient recovery [1]
The inhibitory effects of the different natural royleanones (1-3) were compared in MFC-7, SkBr3, The inhibitory effects of the different natural royleanones (1-3) were compared in MFC-7, SUM159, and SUM159 grown in cancer stem cells (CSCs)-inducing conditions
Summary
Many commercially available chemotherapeutic agents are plant-derived products commercially available chemotherapeutic agents are (e.g., paclitaxel,many vincristine, irinotecan), some may induce resistance andplant-derived toxic effects products that can (e.g., paclitaxel, vincristine, irinotecan), some may induce resistance and toxic effects thatnovel can compromise therapy success and consequent patient recovery [1]. Is still demanded as well the effective drugs with suppressed or lower toxicity on normal cells is still demanded [1], as well as the elucidation of their effect on the modulation of cell death mechanisms and consequent affected elucidation of their on the[2,3]. Has a vast variety of species scattered throughout tropical Africa, Asia, The Plectranthus. Several species have already been been screened for the presence of cytotoxic compounds with notable activities [3,6,7], such as screened formetabolites the presence cytotoxic compounds with activities as secondary secondary ofofditerpenes belonging to thenotable abietane class [3,6,7], [8,9,10]. Several species have already been been screened for the presence of cytotoxic compounds with notable activities [3,6,7], such as screened formetabolites the presence cytotoxic compounds with activities as secondary secondary ofofditerpenes belonging to thenotable abietane class [3,6,7], [8,9,10]. such
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