New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities
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2012
Authors
Krstić, Natalija![](/themes/MirageCER/images/orcid.png)
Bjelaković, Mira
![](/themes/MirageCER/images/orcid.png)
Pavlović, Vladimir D.
Robeyns, Koen
Juranić, Zorica
![](/themes/MirageCER/images/orcid.png)
Matić, Ivana Z.
![](/themes/MirageCER/images/orcid.png)
Novaković, Irena
![](/themes/MirageCER/images/orcid.png)
Sladić, Dušan
![](/themes/MirageCER/images/orcid.png)
Article (Published version)
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Show full item recordAbstract
The reactions of 17 alpha-hydroxyprogesterone with Lawesson's reagent (LR) in toluene, CH2Cl2 and/or CCl4 gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D H-1-C-13 spectra (HSQC and HMBC) and homo-nuclear 2D spectra (NOESY) enabled complete H-1 and C-13 assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-4...53 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia sauna, were evaluated. All tested compounds showed strong antifungal activity.
Keywords:
Phosphorus heterocycle / 17 alpha-Hydroxyprogesterone / Lawesson's reagent / X-ray analysis / 17-Spiro-androstene derivatives / Biological activitySource:
Steroids, 2012, 77, 5, 558-565Publisher:
- Elsevier Science Inc, New York
Funding / projects:
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-MESTD-Basic Research (BR or ON)-172055)
DOI: 10.1016/j.steroids.2012.01.021
ISSN: 0039-128X
PubMed: 22342468
WoS: 000303084000028
Scopus: 2-s2.0-84858335299
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IHTMTY - JOUR AU - Krstić, Natalija AU - Bjelaković, Mira AU - Pavlović, Vladimir D. AU - Robeyns, Koen AU - Juranić, Zorica AU - Matić, Ivana Z. AU - Novaković, Irena AU - Sladić, Dušan PY - 2012 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/945 AB - The reactions of 17 alpha-hydroxyprogesterone with Lawesson's reagent (LR) in toluene, CH2Cl2 and/or CCl4 gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D H-1-C-13 spectra (HSQC and HMBC) and homo-nuclear 2D spectra (NOESY) enabled complete H-1 and C-13 assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-453 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia sauna, were evaluated. All tested compounds showed strong antifungal activity. PB - Elsevier Science Inc, New York T2 - Steroids T1 - New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities VL - 77 IS - 5 SP - 558 EP - 565 DO - 10.1016/j.steroids.2012.01.021 ER -
@article{ author = "Krstić, Natalija and Bjelaković, Mira and Pavlović, Vladimir D. and Robeyns, Koen and Juranić, Zorica and Matić, Ivana Z. and Novaković, Irena and Sladić, Dušan", year = "2012", abstract = "The reactions of 17 alpha-hydroxyprogesterone with Lawesson's reagent (LR) in toluene, CH2Cl2 and/or CCl4 gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D H-1-C-13 spectra (HSQC and HMBC) and homo-nuclear 2D spectra (NOESY) enabled complete H-1 and C-13 assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-453 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia sauna, were evaluated. All tested compounds showed strong antifungal activity.", publisher = "Elsevier Science Inc, New York", journal = "Steroids", title = "New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities", volume = "77", number = "5", pages = "558-565", doi = "10.1016/j.steroids.2012.01.021" }
Krstić, N., Bjelaković, M., Pavlović, V. D., Robeyns, K., Juranić, Z., Matić, I. Z., Novaković, I.,& Sladić, D.. (2012). New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities. in Steroids Elsevier Science Inc, New York., 77(5), 558-565. https://doi.org/10.1016/j.steroids.2012.01.021
Krstić N, Bjelaković M, Pavlović VD, Robeyns K, Juranić Z, Matić IZ, Novaković I, Sladić D. New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities. in Steroids. 2012;77(5):558-565. doi:10.1016/j.steroids.2012.01.021 .
Krstić, Natalija, Bjelaković, Mira, Pavlović, Vladimir D., Robeyns, Koen, Juranić, Zorica, Matić, Ivana Z., Novaković, Irena, Sladić, Dušan, "New androst-4-en-17-spiro-1,3,2-oxathiaphospholanes. Synthesis, assignment of absolute configuration and in vitro cytotoxic and antimicrobial activities" in Steroids, 77, no. 5 (2012):558-565, https://doi.org/10.1016/j.steroids.2012.01.021 . .