Synthesis of Jacaranone-Derived Nitrogenous Cyclohexadienones and Their Antiproliferative and Antiprotozoal Activities
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Physicochemical Properties
2.3. Biological Evaluation
2.3.1. Antiproliferative Activity
2.3.2. Antiprotozoal Activity
2.3.3. Structure-Activity Relationships (SAR) of the Antiproliferative and Antiprotozoal Activity
3. Experimental Section
3.1. Chemicals and Instruments
3.2. Synthesis
3.2.1. General Procedure for the Synthesis of the Compounds, 7a–7j
3.2.2. General Procedure for the Synthesis of the Compounds, 11a–11d
3.2.3. General Procedure for the Reduction of Heterocyclic N-Imides
3.2.4. Procedures for the Synthesis of Dienones, 13a–j, 14a, 14c, 15
3.3. Cytotoxicity against Human (Cancer) Cells
3.3.1. Cell Culture
3.3.2. XTT Viability Assay
3.4. In Vitro Growth Inhibition Assay of Plasmodium Falciparum NF54
3.5. In vitro Growth Inhibition Assay of Trypanosoma Brucei Rhodesiense
3.6. Cytotoxicity against L6 Cells
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 13a–j, 14a, 14c and 15 are available from the authors. |
Compd. | P. falc.a | SI b | T.b.rhod.c | SI b | Cyt. L6 d | Chemical Structure | logP | tPSA (7.4) |
---|---|---|---|---|---|---|---|---|
IC50 (μM) | IC50 (μM) | IC50 (μM) | ||||||
Chl. | 0.002 | |||||||
Mel. | 0.004 | |||||||
Pod. | 0.007 | |||||||
13a | 3.78 | 1.3 | 1.58 | 3.2 | 5.08 | 0.85 | 74.68 | |
13b | 4.42 | 6.1 | 2.15 | 12.5 | 26.80 | −0.18 | 74.68 | |
13c | 8.63 | 1.1 | 6.93 | 1.4 | 9.90 | −0.60 | 74.68 | |
13d | 3.24 | 1.9 | 5.71 | 1.1 | 6.28 | 1.89 | 74.68 | |
13e | 74.38 | 0.1 | 2.26 | 4.5 | 10.26 | −0.38 | 74.68 | |
13f | 28.04 | 5.5 | 44.75 | 3.4 | 153.48 | −0.06 | 87.57 | |
13g | 11.82 | 6.6 | 15.32 | 5.1 | 77.54 | −1.13 | 83.91 | |
13h | 3.04 | 1.0 | 1.70 | 1.7 | 2.96 | 0.81 | 74.68 | |
13i | 1.28 | 2.7 | 0.80 | 4.4 | 3.52 | 0.66 | 74.68 | |
13j | 3.93 | 2.0 | 0.97 | 8.3 | 8.04 | 0.55 | 74.68 | |
14a | 2.91 | 1.0 | 0.57 | 4.9 | 2.81 | 1.89 | 41.74 | |
14c | 10.93 | 0.3 | 0.27 | 12.9 | 3.46 | 0.04 | 49.77 | |
15 | 6.18 | 2.0 | 1.52 | 8.3 | 12.63 | 0.58 | 77.84 |
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Presser, A.; Lainer, G.; Kretschmer, N.; Schuehly, W.; Saf, R.; Kaiser, M.; Kalt, M.-M. Synthesis of Jacaranone-Derived Nitrogenous Cyclohexadienones and Their Antiproliferative and Antiprotozoal Activities. Molecules 2018, 23, 2902. https://doi.org/10.3390/molecules23112902
Presser A, Lainer G, Kretschmer N, Schuehly W, Saf R, Kaiser M, Kalt M-M. Synthesis of Jacaranone-Derived Nitrogenous Cyclohexadienones and Their Antiproliferative and Antiprotozoal Activities. Molecules. 2018; 23(11):2902. https://doi.org/10.3390/molecules23112902
Chicago/Turabian StylePresser, Armin, Gunda Lainer, Nadine Kretschmer, Wolfgang Schuehly, Robert Saf, Marcel Kaiser, and Marc-Manuel Kalt. 2018. "Synthesis of Jacaranone-Derived Nitrogenous Cyclohexadienones and Their Antiproliferative and Antiprotozoal Activities" Molecules 23, no. 11: 2902. https://doi.org/10.3390/molecules23112902