Zao-Sheng Lv

Recent developments of coumarin-containing derivatives and their anti-tubercular activity

Tuberculosis (TB) is a lift-threatening chronic deadliest infectious disease caused predominantly by Mycobacterium tuberculosis (MTB) which affects primarily the lungs (pulmonary TB) apart from other vital organs. The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and the recently cases of totally drug resistant (TDR) towards currently accessible standard drugs was increased up to alarming level in the recent decades. In pursuit of searching new anti-TB agents, numerous of derivatives have been synthesized and screened for their anti-TB activity. Coumarins are one of the most important classes of natural products that exhibited various biological activities, and their derivatives regarded as a new class of effective anti-TB candidates owing to their potential anti-TB activity. Thus, coumarin skeleton has attracted great interest in the development of new anti-TB agents. This review outlines the advances in the application of coumarin-containing derivatives as anti-TB agents and the critical aspects of design and structure-activity relationship of these derivatives.

Isoniazid derivatives and their anti-tubercular activity

Tuberculosis (TB), which has been a scourge of humanity for thousands of years, is a worldwide pandemic disease caused mainly by Mycobacterium tuberculosis (MTB). The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and totally drug-resistant TB (TDR-TB) increase the challenges to eliminate TB worldwide. Isoniazid (INH), a critical frontline anti-TB drug, is one of the most effective drugs used to treatment of TB infection for more than 60 years. Unfortunately, bacterial strains resistant to INH are becoming common which mainly due to the long-term widely use even abuse. Therefore, there is an urgent need to develop novel anti-TB agents. Numerous efforts have been undertaken to develop new anti-TB agents, but no new drug has been introduced for more than 5 decades. It has been suggested that the incorporation of lipophilic moieties into the framework of INH can increase permeation of the drug into bacterial cells, thereby enhancing the anti-TB. Therefore, INH derivatives with greater lipophilicity are emerging as one of the most potential anti-TB agents. Indeed, the INH derivative LL-3858 is in initial stages of phase II clinical trial for the treatment of TB and may be approved to treat TB in the near future. This review aims to summarize the recent advances made towards the discovery anti-TB agents holding INH as a nucleus including INH hybrids and INH hydrazide-hydrazone derivatives.

4-Quinolone hybrids and their antibacterial activities.

The emergence and wide-spread of drug-resistant bacteria including multi-drug resistant and pan-drug resistant pathogens which are associated with considerable mortality, represent a significant global health threat. 4-Quinolones which are exemplified by fluoroquinolones are the second largest chemotherapy agents used in clinical practice for the treatment of various bacterial infections. However, the resistance of bacteria to 4-quinolones develops rapidly and spreads widely throughout the world due to the long-term, inappropriate use and even abuse. To overcome the resistance and improve the potency, several strategies have been developed. Amongst them, molecular hybridization, which is based on the incorporation of two or more pharmacophores into a single molecule with a flexible linker, is one of the most practical approaches. This review aims to summarize the recent advances made towards the discovery of 4-quinolone hybrids as potential antibacterial agents as well as their structure-activity relationship (SAR). The enriched SAR may pave the way for the further rational development of 4-quinolone hybrids with excellent potency against both drug-susceptible and drug-resistant bacteria.

Recent advances of pyrazole-containing derivatives as anti-tubercular agents

One-third of the worlds population infected tuberculosis (TB), and more than 1 million deaths annually. The co-infection between the mainly pathogen Mycobacterium tuberculosis (MTB) and HIV, and the incidence of drug-resistant TB, multi-drug resistant TB, extensively drug-resistant TB as well as totally drug-resistant TB have further aggravated the mortality and spread of this disease. Thus, there is an urgent need to develop novel anti-TB agents against both drug-susceptible and drug-resistant TB. The wide spectrum of biological activities and successful utilization of pyrazole-containing drugs in clinic have inspired more and more attention towards this kind of heterocycles. Numerous of pyrazole-containing derivatives have been synthesized for searching new anti-TB agents, and some of them showed promising potency and may have novel mechanism of action. This review aims to outline the recent achievements in pyrazole-containing derivatives as anti-TB agents and their structure-activity relationship.

Design, synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids

A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-l was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12μg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but were much more toxic (CC50: 7.8-62.5μg/mL) than the parent gatifloxacin (GTFX) (CC50: 125μg/mL). Among them, 61 (MIC: 0.025μg/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0.05μg/mL), GTFX (MIC: 0.78μg/mL) and RIF (MIC: 0.39μg/mL) against MTB H37Rv. The most active conjugate 6k (MIC: 0.06μg/mL) was 16->2048 times more potent than the three references (MIC: 1.0->128μg/mL) against MDR-TB. Both of the two hybrids warrant further investigations.

Asymmetric reduction of prochiral ketones to chiral alcohols catalyzed by plants tissue

As an important organic compound, chiral alcohols are the key chiral building blocks to many single enantiomer pharmaceuticals. Asymmetric reduction of the corresponding prochiral ketones to produce the chiral alcohols by biocatalysis is one of the most promising routes. Asymmetric reduction of different kinds of non-natural prochiral ketones catalyzed by various plants tissue was studied in this work. Acetophenone, 4′-chloroacetophenone and ethyl 4-chloroacetoacetate were chosen as the model substrates for simple ketone, halogen-containing aromatic ketone and β-ketoesters, respectively. Apple (Malus pumila), carrot (Daucus carota), cucumber (Cucumis sativus), onion (Allium cepa), potato (Soanum tuberosum), radish (Raphanus sativus) and sweet potato (Ipomoea batatas) were chosen as the biocatalysts. It was found that these kinds of prochiral ketoness could be reduced by these plants tissue with high enantioselectivity. Both R- and S-form configuration chiral alcohols could be obtained. The e.e. and chemical yield could reach about 98 and 80% respectively for acetophenone and 4′-chloroacetophenone reduction reaction with favorable plant tissue. And the e.e. and yield for ethyl 4-chloroacetoacetate reduction reaction was about 91 and 45% respectively.

Synthesis and In Vitro Antimycobacterial and Antibacterial Activity of 8-OMe Ciprofloxacin-Hydrozone/Azole Hybrids

A series of novel 8-OMe ciprofloxacin (CPFX)-hydrazone/azole hybrids were designed, synthesized, and evaluated for their in vitro biological activities. Our results reveal that all of the hydrozone-containing hybrids (except for 7) show potency against Mycobacterium tuberculosis (MTB) H37Rv (minimum inhibitory concentration (MIC): <0.5 μM), which is better than the parent drug CPFX, and comparable to moxifloxacin and isoniazid, some of the tested Gram-positive strains (MIC: 0.06–4 μg/mL), and most Gram-negative strains (MIC: ≤0.03–4 μg/mL).

Facile fabrication of superhydrophobic coatings based on two silica sols

Superhydrophobic coatings were successfully fabricated by using two silica sols and fluorinated acrylate copolymers through the organic-inorganic hybrid method. The two silica sols contained different nanoparticles, namely, silica nanoparticles with many hydroxyl groups on their surfaces and silica nanoparticles with many long-chain alkyls on their surfaces. The integration of these two silica sols and fluorinated acrylate copolymers satisfied two necessary conditions of multi-scale nano/microstructures and low surface energy for fabricating superhydrophobic coatings. The superhydrophobic surfaces were constructed by using appropriate weight ratios of silica/copolymers and silica sol (methanol) contents. The superhydrophobic coatings displayed a water contact angle as high as 156.2° and contact angle hysteresis of 2.4°, which indicated their good self-cleaning capability. In particular, these coatings showed good mechanical properties and excellent thermal stabilities. The method is not only a facile and inexpensive way to achieve the lotus effect but could also create coatings with high values in practical application.

A green and facile method to fabricate superhydrophobic coatings

ABSTRACT In this work, we reported a green and facile method to fabricate superhydrophobic coatings via blending TiO2 nanoparticles and fluorinated acrylate copolymers. The fluorinated acrylate copolymers were synthesised with the method of solution polymerisation using ethanol as solvent. The integration of TiO2 nanoparticles and the fluorinated acrylate copolymers satisfied two necessary conditions of multi-scale nano/microstructures and low surface energy for fabricating superhydrophobic coatings. It was found that the water contact angle and contact angle hysteresis of the as-prepared coatings were respectively 156.3° and 3.7°, and it indicated that the coatings had excellent superhydrophobicity and self-cleaning ability. In particular, these coatings showed good thermal stabilities. Owing to its flexibility, simplicity and non-toxicity, the method is not only a facile and inexpensive way to achieve the lotus effect but could also create coatings with high values in practical application.