Design, Synthesis and Antibacterial Evaluation of 3-Substituted Ocotillol-Type Derivatives

Abstract

Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives 7–26 were designed and synthesized. The in vitro antibacterial activity was tested on five bacterial strains (B. subtilis 168, S. aureus RN4220, E. coli DH5α, A. baum ATCC19606 and MRSA USA300) and compared with the tests on contrast. Among these derivatives, C-3 position free hydroxyl substituted compounds 7–14, showed good antibacterial activity against Gram-positive bacteria. Furthermore, compound 22 exhibited excellent antibacterial activity with minimum inhibitory concentrations (MIC) values of 2 μg/mL against MRSA USA300 and 4 μg/mL against B. subtilis. The structure-activity relationships of all current ocotillol-type derivatives our team synthesised were summarized. In addition, the prediction of absorption, distribution, metabolism, and excretion (ADME) properties and the study of pharmacophores were also conducted. These results can provide a guide to further design and synthesis works.

Application of Amino Acids in the Structural Modification of Natural Products: A Review

“…Ocotillol enantiopure and its derivatives showed good antibacterial activity anti-gram-positive bacteria (Bi et al, 2015 ; Ren et al, 2019 ), and they can be obtained by the oxidation of PPD with m -CPBA. Wang et al ( 2018 ) introduced free amino groups at the C-3 position to confirm whether the group can enhance the antibacterial activity. The results showed that compound 70 showed excellent antibacterial activity with MIC of 2 μg/mL against MRSA USA300 and 4 μg/mL against B. subtilis .…”

Synthesis and Anti-Hepatocarcinoma Effect of Amino Acid Derivatives of Pyxinol and Ocotillol

“…As for the structure of ocotillol-type sapogenins, 3-OH is relatively far from other hydrogen donor or acceptor atoms and dominates an important place in the metabolic pathway. According to the previous literature, 3-OH was suitable for modification to improve the activity without affecting other potential binding sites [52,53]. Many efforts and progress had been made in modifying 3-OH of ocotillol-type sapogenins.…”

Pyxinol Fatty Acid Ester Derivatives J16 against AKI by Selectively Promoting M1 Transition to M2c Macrophages

“…The R/S stereochemistry at C-24 for ocotillol-type ginsenosides affects the activity of the compound, with the R -configuration having higher activity than the S -configuration . Pyxinol, (20 S ,24 R )-epoxy-dammarane-3 β ,12 β ,25-triol (Figure ) is an ocotillol-type ginsenoside with antitumor, cardioprotective, antimultidrug resistance, and antibacterial effects. , Studies have shown the significance of esterification of pyxinol with fatty acids in structural modifications in enhancing efficacy. , To further enhance the activity of pyxinol, our team used it as a lead compound and introduced saturated fatty acids (C2–C8) to the 3-, 12-, and 25-positions of pyxinol to produce a series of pyxinol fatty acid ester derivatives with new structural skeletons. The structure–activity relationship (SAR) analysis was performed to determine that pyxinol modified by fatty acid ester at the C-3 position had strong anti-inflammatory properties.…”

“…18 Pyxinol, (20S,24R)epoxy-dammarane-3β,12β,25-triol (Figure 1) is an ocotilloltype ginsenoside with antitumor, cardioprotective, antimultidrug resistance, and antibacterial effects. 19,20 Studies have shown the significance of esterification of pyxinol with fatty acids in structural modifications in enhancing efficacy. 21,22 To further enhance the activity of pyxinol, our team used it as a lead compound and introduced saturated fatty acids (C2−C8) to the 3-, 12-, and 25-positions of pyxinol to produce a series of pyxinol fatty acid ester derivatives with new structural skeletons.…”