Synthesis and Antimicrobial Activity Evaluation of Homodrimane Sesquiterpenoids with a Benzimidazole Unit.

Herein we report a feasible study concerning the synthesis and the in vitro antimicrobial activity of some new homodrimane sesquiterpenoids with a benzimidazole unit. Based on some homodrimane carboxylic acids, on their acyl chlorides and intermediate monoamides, a series of seven N-homodrimenoyl-2-amino-1,3-benzimidazoles and 2-homodrimenyl-1,3-benzimidazoles was synthesized. The syntheses involved the decarboxylative cyclization and condensation of the said acids or acyl chlorides with o-phenylendiamine and 2-aminobenzimidazole, as well as the p-TsOH-mediated cyclodehydration of the said monoacylamides. The structures of the synthesized compounds have been fully confirmed, including by the X-ray diffraction. Their biological activities were evaluated on five species of fungi (Aspergillus niger, Fusarium solani, Penicillium chrysogenum, P. frequentans, and Alternaria alternata) and two strains of bacteria (Bacillus sp. and Pseudomonas aeruginosa). Compounds 7 and 20 showed higher antifungal (MIC = 0.064 and 0.05 µg/mL) and antibacterial (MIC = 0.05 and 0.032 µg/mL) activities compared to those of the standards: caspofungin (MIC = 0.32 µg/mL) and kanamycin (MIC = 2.0 µg/mL), and compounds 4, 10, 14, and 19 had moderate activities.

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy.

Nowadays, infectious diseases caused by microorganisms are a major threat to human health, mostly because of drug resistance, multi-drug resistance and extensive-drug-resistance phenomena to microbial pathogens. During the last few years, obtaining hybrid azaheterocyclic drugs represents a powerful and attractive approach in modern antimicrobial therapy with very promising results including overcoming microbial drug resistance. The emphasis of this review is to notify the scientific community about the latest recent advances from the last five years in the field of hybrid azine derivatives with antimicrobial activity. The review is divided according to the main series of six-member ring azaheterocycles with one nitrogen atom and their fused analogs. In each case, the main essential data concerning synthesis and antimicrobial activity are presented.

Synthesis of Homodrimane Sesquiterpenoids Bearing 1,3-Benzothiazole Unit and Their Antimicrobial Activity Evaluation.

Based on some homodrimane carboxylic acids and their acyl chlorides, a series of fourteen 2-homodrimenyl-1,3-benzothiazoles, N-homodrimenoyl-2-amino-1,3-benzothiazoles, 4'-methyl-homodrimenoyl anilides and 4'-methyl-homodrimenthioyl anilides were synthesized and their biological activities were evaluated on five species of fungi (Aspergillus niger, Fusarium solani, Penicillium chrysogenum, P. frequentans, and Alternaria alternata) and two strains of bacteria (Bacillus sp. and Pseudomonas aeruginosa). The synthesis involved the decarboxylative cyclization, condensation and thionation of the said acids, anhydrides or their derivatives with 2-aminothiophenol, 2-aminobenzothiazole, p-toluidine and Lawesson's reagent. As a result, together with the desired compounds, some unexpected products 8, 25, and 27 were obtained, and the structures and mechanisms for their formation have been proposed. Compounds 4, 9, and 25 showed higher antifungal and antibacterial activity compared to the standards caspofungin (MIC = 1.5 µg/mL) and kanamycin (MIC = 3.0 µg/mL), while compound 8 had comparable activities. In addition, compounds 6, 17, and 27 showed selective antifungal activity at MIC = 2.0, 0.25, and 1.0 µg/mL, respectively.

Chemical Composition and Assessment of Antimicrobial Activity of Lavender Essential Oil and Some By-Products.

The producers of essential oils from the Republic of Moldova care about the quality of their products and at the same time, try to capitalize on the waste from processing. The purpose of the present study was to analyze the chemical composition of lavender (Lavanda angustifolia L.) essential oil and some by-products derived from its production (residual water, residual herbs), as well as to assess their "in vitro" antimicrobial activity. The gas chromatography-mass spectrometry analysis of essential oils produced by seven industrial manufacturers led to the identification of 41 constituents that meant 96.80-99.79% of the total. The main constituents are monoterpenes (84.08-92.55%), followed by sesquiterpenes (3.30-13.45%), and some aliphatic compounds (1.42-3.90%). The high-performance liquid chromatography analysis allowed the quantification of known triterpenes, ursolic, and oleanolic acids, in freshly dried lavender plants and in the residual by-products after hydrodistillation of the essential oil. The lavender essential oil showed good antibacterial activity against Bacillus subtilis, Pseudomonas fluorescens, Xanthomonas campestris, Erwinia carotovora at 300 µg/mL concentration, and Erwinia amylovora, Candida utilis at 150 µg/mL concentration, respectively. Lavender plant material but also the residual water and ethanolic extracts from the solid waste residue showed high antimicrobial activity against Aspergillus niger, Alternaria alternata, Penicillium chrysogenum, Bacillus sp., and Pseudomonas aeroginosa strains, at 0.75-6.0 µg/mL, 0.08-0.125 µg/mL, and 0.05-4.0 µg/mL, respectively.

Profiling of Phenolic Compounds and Triterpene Acids of Twelve Apple (Malus domestica Borkh.) Cultivars.

Apple (Malus domestica Borkh.), a popular and widely cultivated fruit world-wide, contains bioactive compounds responsible for their health benefits. Here we report the amounts of some bioactive compounds: two major triterpenes (oleanolic and ursolic acids) and polyphenols (phenolic acids, flavan-3-ols, flavonoids and t-resveratrol), together with bioactive properties of twelve apple cultivars measured by chromatographic and spectrophotometric methods. Significant variations were found comparing the bioactive potential of the investigated cultivars. High contents of phenolic acids were identified in the Montuan, Golden Delicious and Cretesc cultivars, while the most flavonoid dominant was the Richard cultivar. Starkrimson, Jonatan, Beliy Naliv and Richard cultivars present higher antioxidant capacity. Oleanolic acid ranged from 11 to 83 mg/g apple extract, while ursolic acid ranged from 55 to 436 mg/g apple extract, with higher amounts in Richard and Montuan cultivars. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) allowed the discrimination of apple cultivars depending on polyphenolic and triterpene acids composition. Caffeic acid, gallic acid and epicatechin were identified as the main bioactive compounds in Starkrimson, Jonathan, Beliy Naliv and Richard cultivars, while ursolic and oleanolic acids were identified in high amounts in Richard, Montuan, Golden Delicious, Idared and Beliy Naliv apple cultivars. The results obtained in this study will contribute to the understanding of the bioactive composition of apples as well as the importance of their capitalization to obtain value-added products that promote human health.

Bis-(imidazole/benzimidazole)-pyridine derivatives: synthesis, structure and antimycobacterial activity.

Aim: Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Results: Two new classes of bis-(imidazole/benzimidazole)-pyridine derivatives were designed, synthesized and evaluated for their antimycobacterial activity. Conclusion: The synthesis is efficient and straightforward, involving only two successive N-alkylations. The anti-TB assay reveal that our compounds have an excellent anti-TB activity against both replicating and nonreplicating Mtb, are not cytotoxic, exhibited a very good intracellular activity and are active against drug-resistant Mtb strains, some compounds have a bactericidal mechanism. The absorption, distribution, metabolism, excretion and toxicity studies performed for one compound are promising, indicating that it is a good candidate for a future drug.

Minor acetylated metabolites from Euphrasia rostkoviana.

The phenylethanoids rostkovianoside, 6'-O-acetylcrassifolioside and the flavonoid rutin 3‴-acetate, were isolated from the methanolic extract of the aerial parts of Euphrasia rostkoviana Hayne. The structures of these previously undescribed compounds were elucidated by interpretation of spectroscopic data. The acetylation of rutin was also carried out and four ester derivatives were spectroscopically characterized. Finally, a chromatographic method was established to easily identify the acetylated position.

Synthesis, structural elucidation and biological evaluations of new guanidine-containing terpenoids as anticancer agents.

Using sclareol and sclareolide as starting materials, the guanidine derivatives of 12-amino-11-dihomodrimane-8α-ol and 13-amino-14,15-bis-dinorlabd-8(9)-ene were synthesized by the reaction of the corresponding amines with sodium hydrogencyanamide in ethanol - water solution. Monoacyl- and diacylguanidines were prepared from activated with N,N-carbonyldiimidazole Δ8,9-bicyclohomofarnesenoic acid by the reaction with guanidine. Their structures were confirmed by the 1H and 13C NMR, IR spectral and elemental analysis data. The compounds 12, 13 and 15 were screened for their antiproliferative and cytotoxicity activities against Colo 205, Colo 320 and MRC 5 human lung fibroblasts with respect to standard drug, Cisplatin. The compounds 12 and 15 exhibits excellent results than positive control. Hence these two compounds may be act as drug lead molecules in cancer chemotherapy.

Formal synthesis of ( - )-pereniporin B and ( - )-cinnamosmolide.

The paper describes a new pathway for an efficient synthesis of natural and bioactive drimanic compounds ( - )-pereniporin B (1) and ( - )-cinnamosmolide (2) from ketodiol 7, an intermediate obtained before from accessible labdane diterpenoid (+)-larixol (3). The key step involves allylic bromination of acetate 8 with N-bromosuccinimide. The in vitro antimicrobial and antifungal activities of all compounds are also reported. Their structures were confirmed by both spectroscopic data and chemical transformations.