Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1–3 were the most active antiproliferative compounds of the series, with IC₅₀ values in the range of 43.4–46.9 μM and 39.2–48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL⁻¹. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition) at 250 µg∙mL⁻¹ In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL⁻¹.

The properties of two hybrid nanoarchaeosomes (hybrid nanoARCs) made of archaeolipids extracted from the halophilic archaea Halorubrum tebenquichense and combining the properties of archaeolipid bilayers with metallic nanoparticles are explored here. BS-nanoARC, consisting of a nanoARC loaded with yerba mate (Ilex paraguariensis) extract (YME)-biogenic silver nanoparticles (BSs), and [BS + BS-nanoARC], consistent of a BS-nanoARC core covered by an outer shell of BSs, were structurally characterized and their therapeutic activities screened. By employing 109 ± 5 µg gallic acid equivalents (GAEs) and 73.4 µg chlorogenic acid/ YME mg as a silver reductive agent, spherical, heterogeneously sized (~80 nm diameter), −27 mV ζ potential, 90% Ag⁰ and λ_max 420 nm BSs were obtained. We further prepared ~100–200 nm diameter, −57 mV ζ potential BS-nanoARC and ~300 nm diameter, −37 mV ζ potential [BS + BS-nanoARCs]. Freshly prepared and nebulized BS-nanoARCs reduced the release of TNF-α, IL-6 and IL-8 by LPS-irritated THP-1-macrophages and were highly anti-planktonic against S. aureus (MIC₉₀: 13 ± 0.8 µg Ag/mL). While the nanoARCs and BS-nanoARCs were innocuous, freshly prepared [BS + BS-nanoARCs] magnified the cytotoxicity of BSs (IC₅₀ 12 µg Ag/mL vs. IC₅₀ ~36 µg Ag/mL) on A549 cells. Such cytotoxicity remained after 30 days in the dark at 4 °C, while that of BSs was lost. Freshly prepared BSs also lost activity upon nebulization, whereas freshly prepared [BS + BS-nanoARCs] did not. However, the cytotoxicity of the [BS + BS-nanoARCs] was also lost when nebulized after 30 days of storage. Despite the harmful effects of storage and mechanical stress on the structure of the more active [BS + BS-nanoARCs], hybrid nanoARCs are promising examples of nanomedicines combining the properties of archaeolipids with antimicrobial silver nanoparticles and anti-inflammatory polyphenols that could complement oncologic therapies, reducing the usage of classical antitumoral agents, corticosteroids, and, importantly, of antibiotics, as well as their waste.