Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation
| Autor: | Sanja Djokić, Jovana Francuz, Mirjana Popsavin, Marko V. Rodić, Vesna Kojić, Milena Stevanović, Velimir Popsavin |
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| Rok vydání: | 2022 |
| Předmět: |
History
Biological Products Polymers and Plastics Molecular Structure Polyesters X-Rays Organic Chemistry Galactose Antineoplastic Agents Biochemistry Industrial and Manufacturing Engineering Structure-Activity Relationship Cell Line Tumor Polyketides Drug Discovery Humans Business and International Management Drug Screening Assays Antitumor Molecular Biology Cell Proliferation |
| Zdroj: | Bioorganic chemistry. 127 |
| ISSN: | 1090-2120 |
| Popis: | Synthesis of protulactone A (PLA, 1) and twelve of its analogues have been achieved starting from D-galactose. PLA was isolated in the crystalline state, and its crystal structure was determined utilizing X-ray crystallography, which confirmed the assumed stereochemistry at all stereocenters. All tested compounds displayed antiproliferative activity against a panel of tumour cell lines, and all of them were non-cytotoxic toward the normal cells (MRC-5). Natural product PLA (1) was the most active against the K562 and MCF-7 cell lines (IC50 6.52 and 2.20 μM, respectively). Some of the synthesized derivatives showed very potent cytotoxicity, especially analogues 11, 13 and 15 (IC50 1.08–1.14 μM against MCF-7), and 9 and 14 (IC50 1.29 and 1.64 μM against K562). SAR analysis indicated important structural motifs for antiproliferative activity. Unfortunately, PLA (1), its C-7 epimer (2) and demethylated analogue (3) did not display a significant antimicrobial activity (two Gram-positive and two Gram-negative bacteria and one fungal strain) and they also cannot affect the ability to modulate bacterial communication. © 2022 Elsevier Inc. |
| Databáze: | OpenAIRE |
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