Semisynthesis and biological evaluation of some novel Mannich base derivatives derived from a natural lignan obovatol as potential antifungal agents.

Obovatol, a novel lignan isolated from the leaf and stem bark of Magnolia obovata Thunb exhibits many important biological activities. To discover natural-product-based potential fungicides with novel structural skeletons, a series of Mannich base derivatives were prepared by the C-4-aminomethylated modification of obovatol and all synthesized compounds were evaluated for antifungal activities in vitro against several phytopathogenic fungi using the spore germination method and the mycelium growth rate method. Furthermore, their structures were also characterized by 1H NMR, 13C NMR, and HR-MS, and compound 2k was further analyzed by single-crystal X-ray diffraction. Among all of the derivatives, compounds 2b (IC50 = 28.68 µg/mL) and 2g (IC50 = 16.90 µg/mL) demonstrated greater inhibition of Botrytis cinerea spore germination than two positive controls, hymexazol and difenoconazole. Compounds 2c, 2f, and 2g displayed potent mycelial growth inhibition of B. cinerea with an average inhibition rate (AIR) of >90% at a concentration of 100 µg/mL. Additionally, the structure-activity relationships (SARs) suggested that the introduction of a diethylamino, pyrrolyl, 1-methyl-piperazinyl or 1-ethyl-piperazinyl groups on the C-4 position of obovatol may be more likely to yield potential antifungal compounds than the introduction of 4-phenyl-piperazinyl or 4-phenyl-piperidinyl groups.

Identification of mannich base as a novel inhibitor of Mycobacterium tuberculosis isocitrate by high-throughput screening.

Mycobacterium tuberculosis (MTB) remains one of the most significant human pathogens since its discovery in 1882. An estimated 1.5 million people died from tubercle bacillus (TB) in 2006, and globally, there were an estimated 9.27 million incident cases of TB in 2007. Glyoxylate bypass pathway occurs in a wide range of pathogens and plays a key role in the pathogenesis of Mycobacterium tuberculosis. Isocitrate lyase (ICL) can catalyses the first step of this pathway, and reversibly cleaves isocitrate into succinate and glyoxylate. So, ICL may represent a good drug target for the treatment of tuberculosis. ICL was cloned, expressed, and purified, and a high-throughput screen (HTS) developed to screen active molecule from a mannich base compounds library for inhibition of ICL. This assay had signal to noise (S/N) of 650.6990 and Z' factor of 0.8141, indicating that the assay was suitable for HTS. Screening of a collection of 124 mannich base compounds resulted in the identification of one mannich base compound, which has a significant inhibitory activity. So, a new family of compound was first reported to inhibit the activity of Mycobacterium tuberculosis ICL. This family of compound might offer new avenue to explore better anti-tuberculosis and fungi drugs.

Chiral separation of bioactive cyclic Mannich ketones by HPLC and CE using cellulose derivatives and cyclodextrins as chiral selectors.

The chiral separation of cyclic Mannich ketones of potential pharmaceutical interest is investigated using HPLC and CE. These Mannich ketones show a marked antibacterial and antifungal activity. In HPLC, stationary phases containing cellulose derivatives or beta-cyclodextrin were used and in CE different cyclodextrins, such as beta-CD, gamma-CD, carboxymethyl-beta-CD and succinyl-beta-CD were added to the background electrolyte as chiral selectors.