Browsing by Subject "Natural products"

Now showing 1 - 4 of 4

Open Access
Epithelial-to-mesenchymal transition is not a major modulating factor in the cytotoxic response to natural products in cancer cell lines
(MDPI AG, 2021-09-27) Küçükkaraduman, Barş; Çiçek, Ekin Gökçe; Akbar, Muhammad Waqas; Demirkol Canlı, Seçil; Vural, Burçak; Gure, Ali Osmay
Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.
Open Access
Pd-catalyzed synthesis of substituted heteroaromatic fluoranthene analogues and studies towards the total synthesis of truncatone C and imeluteine
(2019-07) Yence, Merve
Fluoranthenes represent an important class of polycyclic aromatic compounds with important applications in modern chemistry and materials science. In addition to being present in the structural core of a variety of fungal natural products, fluoranthenes have also been widely employed as fluorescent probes and in organic electronics. Despite the recent advances in this area, the chemistry of heteroaromatic fluoranthene analogues, in other words, acenaphthylenes fused with heteroaromatic rings such as pyridine, furan, benzofuran, pyrazole, etc. has remained largely unexplored. In this work, we have synthesized a variety of heteroaromatic fluoranthene analogues via a Pd-catalyzed tandem Suzuki-Miyaura and C-H arylation reaction sequence with using different types of boronic acids and esters. Natural products have an undeniable importance in pharmaceutical chemistry, and for the development of new medicinal drugs, natural products and their derivatives still provide significant contribution. In this project, the total synthesis of natural products truncatone C and imeluteine is targeted.
Open Access
Synthesis of the bioactive fungal natural product daldiquinone
(Elsevier Ltd, 2022-05-19) Ahmadli, D.
We report the first total synthesis of the biologically active fungal natural product daldiquinone (5), which was accomplished with a longest linear sequence of 8 steps in 41% overall yield. The construction of the unsymmetrical binaphthalene core was realized by a Suzuki-Miyaura cross-coupling in 88% yield on gram scale. Oxidation of naphthol 17 with IBX afforded the key naphthoquinone intermediate 18 in high yield (92%).
Open Access
Total synthesis of biologically active fungal natural products daldiquinone and bulgarein, and intramolecular Diels-Alder reactions for fluoranthene synthesis
(2021-06) Ahmadlı, Dilgam
Natural products continue to play a significant role in drug discovery and be a substantial source for novel pharmaceutical drugs. Total synthesis of biologically active natural products is critical for deciphering how natural products regulate cellular and other biological processes and, structure determination. In addition, the total synthesis of natural products has also been a stimulus for the discovery of new methodologies and reactions. The fungal natural product daldiquinone (15), which possesses a highly oxidized binaphthyl skeleton, was isolated in 2018 from Daldinia concéntrica, and was shown to have antiangiogenesis activity against HUVECs with an IC50 value of 7.5 M. Another fungal natural product bulgarein (1) was first isolated in 1976 from the fungus Bulgaria inquinans, and was shown to induce topoisomerase I-mediated DNA cleavage. However, as in the case of daldiquinone (15), total synthesis of bulgarein (1) has yet to be reported. In this work, we report the first total syntheses of daldiquinone (15) and bulgarein (1) starting from the commercially available 1,8-DHN (1,8-dihydroxynaphthalene, 1,8-naphthalenediol) via a concise route. Pd-catalyzed Suzuki coupling and C-H arylation reactions between functionalized naphthalenes and hypervalent iodine-mediated double oxidation of phenol to o-quinone were employed as key steps. Thanks to their thermal stability and electronic properties, fluoranthene derivatives have widespread medicinal chemistry and organic optoelectronics applications. A significant number of fluoranthene-based natural products are known, including bulgarein (1). Although many procedures have been developed to synthesize fluoranthenes, practical and modular strategy for synthesizing many substituted unsymmetrical fluoranthenes is still desirable. In this work, we report a novel approach to achieve modular syntheses of fluoranthene derivatives based on intramolecular Diels-Alder reaction.