Antimycobacterial Activity and Immunomodulatory Effects Based in Nitric Oxide Production Inhibitory of Antarctic Seaweeds

Antarctica is known as the most extreme environment on the planet. Extreme environmental conditions, make organisms that have been able to adapt an important source for the discovery of bioactive substances. Sessile organisms such as seaweeds are known to produce secondary metabolites with potential for treating several diseases caused by microorganisms. Tuberculosis, produced by Mycobacterium tuberculosis, is the leading cause of death worldwide from an infectious disease agent. The emergence of multi-resistant strains makes finding new substances necessary to control the disease. This work aims to investigate the potential for the treatment of tuberculosis, evaluating the antimycobacterial and immunomodulatory activity (based on NO inhibition). Twenty-seven seaweeds of the phylum Chlorophyta (7.4%), Ochrophyta (22.2%) and Rhodophyta (70.4%), were collected during the XXXVI Operantar (Brazilian Antarctic Operation) with the support of the Brazilian Navy between November and December 2017 in five locations along the South Shetland Islands, Antarctica. The lyophilized material was extracted with MeOH: EtOAc 1:1 and the chemical profiles were investigated by chromatographic and spectrometric techniques. The antimycobacterial activity was evaluated against the Mtb H37Rv and Mtb M299 and compared with the anti-TB drug rifampicin. Suspensions of Mtb H37Rv and Mtb M299 in culture medium were incubated with crude extracts (0.8-100 μg/mL) for 5 days. LPS-stimulated RAW 264.7 macrophages were treated with the same samples for 24 hours to assess cytotoxicity and inhibition of NO production. The yield of the extracts varied from 0.34 to 16.85%. Of the seaweed analyzed, 59.3% of the extracts presented IC50 below 20 µM/mL against Mtb H37Rv and 33.3% an IC50 below 20 µM/mL against Mtb M299. Six samples with dual activity and selectivity index greater than 10 were selected as promising, all with an IC50 <10 µM/mL against Mtb H37Rv. Pyropia endiviifolia was the most active extract in mycobacterial growth-inhibiting against Mtb H37Rv (IC90 15.3 ± 1.3 µg/mL) and Mtb M299 (IC90 50.6 ± 1.3 μg/mL) and NO production (IC50 6.8 ± 1.3 μg/mL). The chemical profiles analysis showed substances belonging to different classes of natural products such as fatty acids, sterols, alkaloids and terpenes in the active samples. Intraspecific variations were observed depending on the collection site for both the chemical profile and the antimycobacterial activity. Antarctic seaweeds produce substances with antimycobacterial potential, which makes them excellent candidates for the elucidation of new bioactive substances.