Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation
Апстракт
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.
Кључне речи:
X-ray analysis / Protulactone A / Natural product / Bicyclic lactone / Antiproliferative activity / Antimicrobial activityИзвор:
Bioorganic Chemistry, 2022, 127Издавач:
- Academic Press Inc.
Финансирање / пројекти:
- Синтеза и биолошка испитивања нових миметика или деривата одабраних цитотоксичних лактона, антитуморског агенса тиазофурина и природних нафтних киселина (RS-MESTD-Basic Research (BR or ON)-172006)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200125 (Универзитет у Новом Саду, Природно-математички факултет) (RS-MESTD-inst-2020-200125)
DOI: 10.1016/j.bioorg.2022.105980
ISSN: 0045-2068
PubMed: 35772366
Scopus: 2-s2.0-85132916402
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Đokić, S. AU - Francuz, J. AU - Popsavin, M. AU - Rodić, M.V. AU - Kojić, V. AU - Stevanović, Milena AU - Popsavin, V. PY - 2022 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1546 AB - 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. PB - Academic Press Inc. T2 - Bioorganic Chemistry T1 - Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation VL - 127 DO - 10.1016/j.bioorg.2022.105980 ER -
@article{ author = "Đokić, S. and Francuz, J. and Popsavin, M. and Rodić, M.V. and Kojić, V. and Stevanović, Milena and Popsavin, V.", year = "2022", abstract = "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.", publisher = "Academic Press Inc.", journal = "Bioorganic Chemistry", title = "Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation", volume = "127", doi = "10.1016/j.bioorg.2022.105980" }
Đokić, S., Francuz, J., Popsavin, M., Rodić, M.V., Kojić, V., Stevanović, M.,& Popsavin, V.. (2022). Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation. in Bioorganic Chemistry Academic Press Inc.., 127. https://doi.org/10.1016/j.bioorg.2022.105980
Đokić S, Francuz J, Popsavin M, Rodić M, Kojić V, Stevanović M, Popsavin V. Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation. in Bioorganic Chemistry. 2022;127. doi:10.1016/j.bioorg.2022.105980 .
Đokić, S., Francuz, J., Popsavin, M., Rodić, M.V., Kojić, V., Stevanović, Milena, Popsavin, V., "Natural product protulactone A: Total synthesis from D-galactose, X-ray analysis and biological evaluation" in Bioorganic Chemistry, 127 (2022), https://doi.org/10.1016/j.bioorg.2022.105980 . .