No abstract

Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.

Ocotillol-type saponins have a wide spectrum of biological activities. Previous studies indicated that the configuration at the C24 position may be responsible for their stereoselectivity in pharmacological action and pharmacokinetics. Natural ocotillol-type saponins share a 20(S)-form but it has been found that the 20(R)-stereoisomers have different pharmacological effects. The semisynthesis of 20(R)-ocotillol-type saponins has not been reported and it is therefore worthwhile clarifying their crystal structures. Two C24 epimeric 20(R)-ocotillol-type saponins, namely (20R,24S)-20,24-epoxydammarane-3β,12β,25-triol, C30H52O4, (III), and (20R,24R)-20,24-epoxydammarane-3β,12β,25-triol monohydrate, C30H52O4·H2O, (IV), were synthesized, and their structures were elucidated by spectral studies and finally confirmed by single-crystal X-ray diffraction. The (Me)C-O-C-C(OH) torsion angle of (III) is 146.41 (14)°, whereas the corresponding torsion angle of (IV) is -146.4 (7)°, indicating a different conformation at the C24 position. The crystal stacking in (III) generates an R4(4)(8) motif, through which the molecules are linked into a one-dimensional double chain. The chains are linked via nonclassical C-H...O hydrogen bonds into a two-dimensional network, and further stacked into a three-dimensional structure. In contrast to (III), epimer (IV) crystallizes as a hydrate, in which the water molecules act as hydrogen-bond donors linking one-dimensional chains into a two-dimensional network through intermolecular O-H...O hydrogen bonds. The hydrogen-bonded chains extend helically along the crystallographic a axis and generate a C4(4)(8) motif.

Introduction: To determine the phenotypes and genotypes of invasive Streptococcus pneumoniae (S. pneumoniae), 108 strains were isolated from paediatric patients with invasive pneumococcal diseases (IPDs) in Shenzhen from 2014 to 2018. Methods: Serotype profiles were defined by multiplex PCR of the capsule gene. Pneumococcal surface protein A (PspA) classification was performed through pspA gene sequencing. Antimicrobial resistance was examined by broth microdilution. Multilocus sequence typing (MLST) was determined based on next-generation sequencing data. Results: Eighty-one S. pneumoniae of 17 serotypes were finally collected. The coverage of the 13-conjugated polysaccharide vaccine (PCV13) was 88.9%. After the introduction of PCV13, the nonvaccine serotypes were added by serotypes 15b, 16F and 20. Vaccine serotype 3 increased by four serious cases. The pspA family 1 and pspA family 2 are predominant. The multiple drug resistance rate is 91.3%. None of the nonmeningitis isolates were resistant to penicillin, while 98.8% of all the isolates were resistant to erythromycin. Discussion: This work characterizes the molecular epidemiology of invasive S. pneumoniae in Shenzhen. Continued surveillance of serotype distribution and antimicrobial susceptibility is necessary to alert antibiotic-resistant nonvaccine serotypes and highly virulent serotypes.

In order to study the in vivo protective effect on myocardial ischemia, (20S,24R)-epoxydammarane-12β,25-diol, (V), and (20S,24S)-epoxydammarane-12β,25-diol, (VI), were synthesized through a novel synthetic route. Two key intermediates, namely (20S,24R)-3-acetyl-20,24-epoxydammarane-3β,12β,25-triol, (III) [obtained as the hemihydrate, CHO·0.5HO, (IIIa), and the ethanol hemisolvate, CHO·0.5CHOH, (IIIb), with identical conformations but different crystal packings], and (20S,24S)-3-acetyl-20,24-epoxydammarane-3β,12β,25-triol, CHO, (IV), were obtained during the synthesis. The structures were confirmed by H NMR,C NMR and HRMS analyses, and single-crystal X-ray diffraction. Molecules of (IIIa) are extended into a two-dimensional network constructed with water molecules linked alternately through intermolecular O-H...O hydrogen bonds, which are further stacked into a three-dimensional network. Compound (IIIb) contains two completely asymmetric molecules, which are linked in a disordered manner through intermolecular C-H...O hydrogen bonds. While the crystal stacks in compound (IV) are linked via weak C-H...O hydrogen bonds, the hydrogen-bonded chains extend helically along the crystallographic b axis.