New Antiproliferative Polyunsaturated Epoxy-Heneicosane Derivatives Isolated from the Brown Alga <i>Lobophora variegata</i>

Two new polyunsaturated 3,4-epoxy-heneicosane derivatives named as epoxy-lobophorene A and epoxy-lobophorene B were isolated from the brown alga Lobophora variegata, in addition to nine known compounds. The structures of the new compounds were elucidated using a combination of 1D/2D nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS). The isolated compounds were submitted to antiproliferative assays against the human colon cancer cell line HCT-116, human metastatic prostate cancer PC-3M, murine metastatic melanoma B16-F10 and murine fibroblast cell line L929 and also tested as antibacterial. Both 3,4-epoxy lobophorene A and 3,4-epoxy lobophorene B depicted moderate antiproliferative effect against cell lines. None of them showed antibacterial activity.

Keywords:
Lobophora variegata; brown algae; 3,4-epoxy lobophorenes; antiproliferative activity

Authorship

Fábio N. Ávila

Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, 60021-970, Fortaleza-CE, BrazilUniversidade Federal do CearáBrazilFortaleza, CE, BrazilDepartamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, 60021-970, Fortaleza-CE, Brazil

Francisco C. L. Pinto

Pedro B. M. Carneiro

Campus Ministro Reis Velloso, Universidade Federal do Piauí, 64202-020 Parnaíba-PI, BrazilUniversidade Federal do PiauíBrazilParnaíba, PI, BrazilCampus Ministro Reis Velloso, Universidade Federal do Piauí, 64202-020 Parnaíba-PI, Brazil

http://orcid.org/0000-0002-4577-3803

Kayanny Q. Ferreira

Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, 60430-275 Fortaleza-CE, BrazilUniversidade Federal do CearáBrazilFortaleza, CE, BrazilDepartamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, 60430-275 Fortaleza-CE, Brazil

Diego V. Wilke

Nádia A. P. Nogueira

Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, 60430-370, Fortaleza-CE, BrazilUniversidade Federal do CearáBrazilFortaleza, CE, BrazilDepartamento de Análises Clínicas e Toxicológicas, Universidade Federal do Ceará, 60430-370, Fortaleza-CE, Brazil

Edilberto R. Silveira

http://orcid.org/0000-0003-4178-0296

Otília Deusdênia L. Pessoa ^**e-mail: otilialoiola@gmail.com

*e-mail: otilialoiola@gmail.com

SCIMAGO INSTITUTIONS RANKINGS

Figures | Tables

Figures (3)
Tables (3)

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Figure 1
Structures of the isolated compounds from Lobophora variegata: 3,4-epoxy-lobophorene A (1); 3,4-epoxy-lobophorene B (2); β-carotene (3); fucosterol (4); apo-9’-fucoxanthinone (5); apo-13’-fucoxanthinone (6); lobophorenol B (7); phytene glyceryl ether (8); hepoxylin derivative (7,8-HepETE, 9); loliolide (10) and isololoilide (11).

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Figure 2
Important COSY (—) and HMBC (⃕) correlations.

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Scheme 1
Suggested approach for the biosynthetic pathway of compounds 1 and 2.

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Table 1
¹H and ¹³C NMR data comparison of compounds 1 and 2 (δ in ppm, CDCl₃, 500 MHz)

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Table 2
Antiproliferative activity of compounds 1-11 on a human tumor cell line (HCT-116) by MTT assay after 72 h incubation

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Table 3
Antiproliferative activity of compounds 1 and 2 on a panel of cell lines by sulforhodamine B (SRB) assay

Figure 1 Structures of the isolated compounds from Lobophora variegata: 3,4-epoxy-lobophorene A (1); 3,4-epoxy-lobophorene B (2); β-carotene (3); fucosterol (4); apo-9’-fucoxanthinone (5); apo-13’-fucoxanthinone (6); lobophorenol B (7); phytene glyceryl ether (8); hepoxylin derivative (7,8-HepETE, 9); loliolide (10) and isololoilide (11).

Figure 2 Important COSY (—) and HMBC (⃕) correlations.

Scheme 1 Suggested approach for the biosynthetic pathway of compounds 1 and 2.

Table 1 ¹H and ¹³C NMR data comparison of compounds 1 and 2 (δ in ppm, CDCl₃, 500 MHz)

	1 (CDCl₃, J in Hz)		2 (CDCl₃, J in Hz)
	δ _C	δ _H	δ _C	δ _H
1	120.6	5.51 (m), 5.38 (m)	10.8	1.06 (t, 7.6)
2	132.4	5.75 (m)	21.2	1.62 (m), 1.55 (m)
3	57.2	3.44 (dd, 6.8, 4.2)	58.5	2.98 (dt, 6.4, 4.3)
4	58.1	3.10 (td, 6.3, 4.2)	56.7	2.91 (dt, 6.2, 4.3)
5	26.4	2.41 (dt, 14.8, 6.6)	26.3	2.43 (td, 13.8, 6.3)
		2.25 (dt, 14.8, 6.5)		2.24 (td, 13.9, 6.5)
6	124.3	5.45 (m)	124.7	5.50 (m)
7	130.9	5.48 (m)	130.6	5.50 (m)
8	25.8	2.85^a a Overlapping of signals.	25.8	2.85^a a Overlapping of signals.
9	128.7	5.38^a a Overlapping of signals.	128.7	5.37^a a Overlapping of signals.
10	128.7	5.38^a a Overlapping of signals.	128.6	5.37^a a Overlapping of signals.
11	26.0	2.85^a a Overlapping of signals.	26.0	2.85^a a Overlapping of signals.
12	128.1	5.38^a a Overlapping of signals.	128.1	5.37^a a Overlapping of signals.
13	128.0	5.38^a a Overlapping of signals.	128.0	5.37^a a Overlapping of signals.
14	25.8	2.85^a a Overlapping of signals.	25.8	2.85^a a Overlapping of signals.
15	127.9	5.38^a a Overlapping of signals.	127.9	5.37^a a Overlapping of signals.
16	130.2	5.38^a a Overlapping of signals.	130.2	5.40 (m)
17	26.8	2.09 (m)	26.8	2.09 (m)
18	29.0	1.46 (quint, 7.4)	29.0	1.47 (quint, 7.5)
19	33.5	2.09 (m)	33.5	2.06 (quint, 6.8)
20	138.9	5.82 (m)	138.9	5.82 (m)
21	114.7	5.03 (m)	114.7	5.02 (dd, 17.2, 1.2)
		4.96 (m)		4.96 (dd, 10.2, 0.9)

^a
Overlapping of signals.

Table 2 Antiproliferative activity of compounds 1-11 on a human tumor cell line (HCT-116) by MTT assay after 72 h incubation

Compound	IC₅₀ (CI 95%) / µM
1	12.2 (7.1 to 21.1)
2	44.3 (30.0 to 65.0)
3	–
4	> 120
5	> 180
6	50.0 (22.3 to 112.0)
7	23.4 (10.0 to 55.0)
8	41.5 (4.5 to 375.0)
9	84.5 (48.6 to 147.0)
10	> 250
11	> 250
Doxorubicin^a a Doxorubicin was used as positive control. Data are presented as inhibition concentration mean values (IC50) with their confidence intervals of 95% (CI 95%) obtained by non-linear regression. Experiments were performed in triplicate. MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide.	0.4 (0.2 to 0.6)

^a
Doxorubicin was used as positive control. Data are presented as inhibition concentration mean values (IC₅₀) with their confidence intervals of 95% (CI 95%) obtained by non-linear regression. Experiments were performed in triplicate. MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide.

Table 3 Antiproliferative activity of compounds 1 and 2 on a panel of cell lines by sulforhodamine B (SRB) assay

Compound	Effect^a a The effects are depicted as growth inhibition mean (GI50), total growth inhibition (TGI) and lethal concentration mean (LC50) values in µM obtained by interpolation of non-linear regression;	Tumor cell line^b b the human colon adenocarcinoma (HCT-116), human metastatic prostate cancer (PC-3M), murine metastatic melanoma (B16-F10) and murine fibroblast cell line (L929) were treated with compounds 1 and 2 with concentrations ranging from 0.01 to 335 µM during 72 h incubation. Experiments were performed in duplicate.			Fibroblast cell line^b b the human colon adenocarcinoma (HCT-116), human metastatic prostate cancer (PC-3M), murine metastatic melanoma (B16-F10) and murine fibroblast cell line (L929) were treated with compounds 1 and 2 with concentrations ranging from 0.01 to 335 µM during 72 h incubation. Experiments were performed in duplicate.
Compound		HCT-116	PC-3M	B16-F10	L929
1	GI₅₀	8.6	16.6	38.2	5.3
	TGI	103.7	> 168	109.4	158.1
	LC₅₀	> 335	> 168	313.0	> 335
2	GI₅₀	8.1	7.4	26.7	1.6
	TGI	93.1	> 168	69.8	23.6
	LC₅₀	> 335	> 168	182.5	> 335

^a
The effects are depicted as growth inhibition mean (GI₅₀), total growth inhibition (TGI) and lethal concentration mean (LC₅₀) values in µM obtained by interpolation of non-linear regression;
^b
the human colon adenocarcinoma (HCT-116), human metastatic prostate cancer (PC-3M), murine metastatic melanoma (B16-F10) and murine fibroblast cell line (L929) were treated with compounds 1 and 2 with concentrations ranging from 0.01 to 335 µM during 72 h incubation. Experiments were performed in duplicate.

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New Antiproliferative Polyunsaturated Epoxy-Heneicosane Derivatives Isolated from the Brown Alga <i>Lobophora variegata</i>

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[1] *e-mail: otilialoiola@gmail.com