Commiphora leptophloeos is a plant specie usually known for its medicinal purposes in local communities in Northeast Brazil. In order to evaluate its therapeutic potential, we aimed to determine the phytochemical and antimicrobial properties of C. leptophloeos extracts. Thin Layer Chromatography (TLC) was able to detect the presence of phenolic compounds, flavonoids and reducing sugars. Three phenolic compounds were identified by HPLC and described as Gallic, Chlorogenic and Protocatechuic acids. On the other hand, H1NMR analysis revealed the presence of hinokinin, a bioactive lignan further characterized in the present work. The minimum inhibitory concentration (MIC) values for hinokinin ranged from 0.0485 to 3.125 mg/mL in different S. aureus clinical isolates and showed a bactericidal activity against MRSA isolated from blood (MMC 0.40 mg/mL) and postoperative secretion (MMC = 3.125 mg/mL). C. leptophloeos extracts also showed antimicrobial activity against Mycobacterium species such as M. smegmatis (MIC = 12.5 mg/mL) and M. tuberculosis (MIC = 52 mg/mL). Additionally, we determined the toxicity of C. leptophloeos by in vitro HC50 tests with hemolytic activity detected of 313 ± 0.5 μg/mL. Our results showed that C. leptophloeos possesses inhibitory properties against MRSA as well as several other clinically important microorganisms. Furthermore, the present work is the first report of the presence of hinokinin in Commiphora genus.

Click chemistry-based strategies for the synthesis of 2-amino-alkyl-1,2,3-triazole-1,4-naphthoquinone derivatives make it possible to obtain desired products from 1,4-naphthoquinone (1,4-NQ), and bio-based lawsone, nor-lapachol and lapachol. The first route (Strategy A) starting from 1,4-NQ and amino alcohols, then 2-amino-alkyl-1,4-NQ alcohols, were tosylated. The azide ion displaced the tosylate group to afford 2-azide-alkyl-1,4-NQ, which was submitted to a copper-catalyzed azide alkyne cycloaddition (CuAAC) condition. The triazole-naphthoquinones were obtained in an overall yield of roughly 47%. Another pathway (Strategy B) substituted bromo-alkyl-phthalimides using NaN 3 as the nucleophile, sequential CuAAC and deprotection of phthalimide group with hydrazine producing amino-triazoles. The subsequent reaction with 1,4-NQ produced 2-amino-alkyl-1,2,3-triazole-1,4-NQ derivatives in an overall yield of 45-76% in four steps. After we developed these two strategies, linear synthesis (Strategy A) was chosen to prepare 2-[(2-(1H-1,2,3-triazol-1-yl)ethylamino)]-3-(3-methylpropenyl)-1,4-naphthoquinones from lawsone with an overall yield of approximately 27% in six steps. On the other hand, convergent synthesis (Strategy B) was employed for the synthesis of 2-[(4-phenyl-1H-1,2,3-triazol-1-yl)alkylamino)]-3-(3-methylbut-2-en-1-yl)-1,4-naphthoquinones from the reaction between 2-methoxylapachol with amino-triazoles with a global yield of about 21%. These synthetic strategies might lead us to new opportunities to build small-molecule libraries for future biological exploration.Keywords: click chemistry, amino-naphthoquinone, lapachol, nor-lapachol, 1,2,3-triazole IntroductionThe synthesis of New Chemical Entities (NCE) remains unaffected by changes in the focus of chemical science. 1A number of synthetic strategies have been developed recently to allow organic chemists to create a great variety of molecules. In order to access novel and diverse chemical libraries of compounds with potential biological activity the use of catalytic methods is prominent.From a synthetic point of view, the Huisgen 1,3-dipolar cycloaddition reaction between organic azides and terminal alkynes has been a straightforward method to assemble a large number of molecules, especially since Sharpless and co-workers 2 and Meldal and co-workers 3 proposed the copper-catalyzed azide-alkyne cycloaddition (CuAAC). This protocol has permitted easy access to molecular diversity of 1,2,3-triazoles and encouraged synthetic chemists to design projects based on this scaffold. [4][5][6][7][8][9][10][11] This reaction has provided the opportunity to synthesize molecules having new properties or biological activities, 12,13 including anti-tuberculosis, 14 antiviral, 15 antitumoral, [16][17][18] antifungal, 19 antibiotic (e.g., tazobactam, see Figure 1a), 20 among others, as can be found in the literature. 21 Moreover, naphthoquinones moieties such as potent trypanocidal and leishmanicidal activities have been synthesized (Figure 1a). [22][23][24] S i n c e m o l ...

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