Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Study on the modification and anti-tumor activity of silybin derivatives for CDK4/6 targeted / 药学学报

By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, 13C NMR and 1H NMR. The in vitro antitumor activity evaluation of the target compound was carried out by MTT method, and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells (HepG-2). Experimental results show that all compounds are higher than the activity of the parent silybin, of which compound I1 has a certain inhibitory effect on human HepG-2 cells, which is worth further study.

Microbial transformation of artemisinin and its derivatives / 中国中药杂志

Microbial transformation is an efficient enzymatic approach for the structural modification of exogenous compounds to obtain derivatives. Compared with traditional chemical synthesis, the microbial transformation has in fact the undoubtable advantages of strong region-and stereo-selectivity, and a low environmental and economic impact on the production process, which can achieve the reactions challenging to chemical synthesis. Because microbes are equipped with a broad-spectrum of enzymes and therefore can metabolize various substrates, they are not only a significant route for obtaining novel active derivatives, but also an effective tool for mimicking mammal metabolism in vitro. Artemisinin, a sesquiterpene with a peroxy-bridged structure serving as the main active functional group, is a famous antimalarial agent discovered from Artemisia annua L. Some sesquiterpenoids, such as dihydroartemisinin, artemether, and arteether, have been developed on the basis of artemisinin, which have been successfully marketed and become the first-line antimalarial drugs recommended by WHO. As revealed by pharmacological studies, artemisinin and its derivatives have exhibited extensive biological activities, including antimalarial, antitumor, antiviral, anti-inflammatory, and immunomodulatory. As an efficient approach for structural modification, microbial transformation of artemisinin and its derivatives is an increasingly popular strategy that attracts considerable attention recently, and numerous novel derivatives have been discovered. Herein, this paper reviewed the microbial transformation of artemisinin and its artemisinin, including microbial strains, culture conditions, product isolation and yield, and biological activities, and summarized the advances in microbial transformation in obtaining active derivatives of artemisinin and the simulation of in vivo metabolism of drugs.

Synthesis and antibacterial activity of water-soluble limonin benzoylhydrazone derivatives / 中国药科大学学报

@#As a compound rich in citrus plants, limonin has a wide range of biological activities, but its practical application is limited because of its poor water solubility.In this paper, eight new compounds 7a-7h were designed and synthesized by introducing benzoyl hydrazone at the carbonyl position of limonin.The results showed that the water solubilities of all compounds were higher than that of limonin, especially 7a, 7d, 7e and 7f.In addition, the experiment showed that compounds 7d and 7e with substituted hydroxyl groups at the interposition and para-position of the benzene ring had strong antibacterial effects against Escherichia coli and Staphylococcus aureus, and that compound 7e had the best activity, with minimum inhibitory concentrations of 0.31 mg/mL and 1.25 mg/mL, respectively.And compound 7e had better antibacterial activiy in E.coli than sodium benzoate.

Synthesis, and anti-inflammatory activities of gentiopicroside derivatives / 中国天然药物

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Design and semisynthesis of oleanolic acid derivatives as VEGF inhibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs / 中国天然药物

Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,β-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.

Old fusidane-type antibiotics for new challenges: Chemistry and biology / 中国天然药物

The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future. To deal with these "new challenges", scientists tend to re-pick up "old antibiotics". Fusidane-type antibiotics have been known for nearly 80 years as potent antibacterial agents against gram-positive bacteria, especially Staphylococci, and represent the only triterpene-derived antibiotic class in clinical setting. These attractive characteristics have drawn renewed attention on fusidane-type antibiotics in recent decades. Isolation, characterization, biological evaluation, as well as chemical modifications of fusidane-type antibiotics are increasingly being reported. Combinatorial biosynthesis of this type of antibiotics has been successfully utilized not only for elucidating the biosynthetic pathways, but also for expanding their structural diversity. Some isolated and synthetic compounds exhibit comparable or even more potent biological activity than fusidic acid. This review provides an overview of progress on the studies of structure and biology of fusidane-type antibiotics from 1943 to April 2021. The informative structure-activity relationship is also highlighted.

Advances in the study of structural modification and biological activities of asiatic acid / 药学学报

Asiatic acid (AA) is a ursane pentacyclic triterpenoids, which possesses a wide range of pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory, anti-bacterial. Due to poor solubility and low bioavailability, clinical application of asiatic acid is limited. To address these defects, the structural modifications of AA have been carried out, and large numbers of AA-based derivatives with novel structure and eximious biological activity have been developed. In this paper, the research progress of structural modifications, biological activity, structure-activity relationship and mechanism studies in recent twenty years are reviewed, which provides reference for development of AA-related drugs.

Recent progress on betulinic acid and its derivatives as antitumor agents: a mini review / 中国天然药物

Natural products are one of the important sources for the discovery of new drugs. Betulinic acid (BA), a pentacyclic triterpenoid widely distributed in the plant kingdom, exhibits powerful biological effects, including antitumor activity against various types of cancer cells. A considerable number of BA derivatives have been designed and prepared to remove their disadvantages, such as poor water solubility and low bioavailability. This review summarizes the current studies of the structural diversity of antitumor BA derivatives within the last five years, which provides prospects for further research on the structural modification of betulinic acid.

Application of sucrose phosphorylase in glycosylation / 生物工程学报

Water solubility, stability, and bioavailability, can be substantially improved after glycosylation. Glycosylation of bioactive compounds catalyzed by glycoside hydrolases (GHs) and glycosyltransferases (GTs) has become a research hotspot. Thanks to their rich sources and use of cheap glycosyl donors, GHs are advantageous in terms of scaled catalysis compared to GTs. Among GHs, sucrose phosphorylase has attracted extensive attentions in chemical engineering due to its prominent glycosylation activity as well as its acceptor promiscuity. This paper reviews the structure, catalytic characteristics, and directional redesign of sucrose phosphorylase. Meanwhile, glycosylation of diverse chemicals with sucrose phosphorylase and its coupling applications with other biocatalysts are summarized. Future research directions were also discussed based on the current research progress combined with our working experience.

Research advances on structural modifications to resveratrol and their effect on biological activities / 药学学报

Resveratrol possesses a wide range of biological activities, such as anti-cancer, anti-oxidation, induction of apoptosis, etc., but its poor drug properties, rapid metabolism, low target selectivity and bioavailability limit its application value. Studies have shown that modification of the structure of natural compounds can improve their pharmacological activities. To improve the bioavailability of resveratrol, many researchers have undertaken the synthesis and activity evaluation of resveratrol derivatives and analogues. They have modified the phenolic hydroxyl groups, double bonds and benzene ring of resveratrol so as to further understand the interactions among functional groups and its structure-activity relationship. In this paper, we review the chemical structures, synthetic methods and mechanisms of biological activity of resveratrol monomer derivatives as well as their related therapeutic applications, especially in the anticancer area over the last decade. This will provide some reference value for the further research and development of resveratrol-related drugs.

Research progress on anti-tumor activity of curcumol and its derivatives / 中草药

Curcumol, as an important component of Curcuma Rhizoma, has anti-virus, anti-inflammatory, anti-tumor and other pharmacological activities, which has attracted more and more attentions in anti-tumor research area. The progress on the natural source, anti-tumor mechanism, structural modification, and anti-tumor evaluation of curcumol are reviewed in this paper, which will provide a novel strategy for its further structural optimization.

Structural Modification and Biological Activity of Piperlongumine / 中国药学杂志

The piperlongumine is a tertiary amine amide alkaloid, which is mainly found in the roots of the Piper family like long piper (Piper longum L.) and tumor-like piper (Piper tuberculatum Jacq). It has a variety of pharmacological activities, such as anti-platelet aggregation, anti-inflammatory and anti-tumor and its derivatives also have a variety of activities. In this paper, the research progress on the structural modification and bioactivity of pharmacological effects of the piperlongumine amide is reviewed, which provides a reference for the further study of amides.

Paeonol derivatives and their pharmacological activities / 中草药

Paeonol has a wide range of pharmacological activities. It is mainly used to protect cardiovascular and cerebrovascular system, promote microcirculation, antibacterial and anti-inflammatory, antitumor, anti-oxidation, anti-allergic reaction, enhance immunity, and treat diabetic osteoporosis, etc. In recent years, it not only improves the method of artificially synthesizing paeonol, but also carries out a large number of structural modification and transformation of paeonol. Five major parts, carbonyl, phenolic hydroxyl, carbonyl α-H, methoxy, and benzene rings, have been mainly modified. About 16 kinds of paeonol derivatives were produced including carboxylic acid esters, sulfonates esters, phosphates esters, ethers, NO donors, glycosidation, paeonol sodium, Schiff bases, thiazoles, oximes, hydroxyalkylation, α,β-unsaturated ketones, aminomethylation, α-H halogenation, demethylation, and benzene ring halogenation. In this paper, the derivatives of paeonol and their pharmacological activities were reviewed in combination with the literatures on paeonol derivatives at home and abroad. This article may provide basis for further study of this type of compound.

Synthesis and antitumor evaluation of sophocarpine-cinnamic acid ester derivatives as potential antitumor agents / 中草药

Objective: To synthesize sophocarpine-cinnamic acid ester derivatives and evaluate the in vitro antitumor activities of the derivatives. Methods: Taking sophocarpine as the starting material, the target compounds were synthesized by oxidation, esterification, N-alkylation, reduction, condensation, hydrolysis, and salification. Their antitumor activities in vitro were evaluated for HeLa, HepG2 and A-549 by MTT assay. Results: Eleven sophocarpine-cinnamic acid ester derivatives were synthesized and the structures were characterized by 1H-NMR, 13C-NMR and HRMS. MTT assay showed that some derivatives exhibited good antitumor activities. Compound 5g showed good antitumor activity against three human tumor cell lines, which was better than that of the positive control drug, cisplatin. Conclusion: Some derivatives showed promising antitumor activities and compound 5g was worth further studying.

Research progress on glycosidation modification of catechins / 中草药

Catechins, the main component of tea health care function, are flavonoids with strong physiological activities, such as broad spectrum bacteriostatic activity, anti-mutation, anti-cancer effects and the protection of the nervous system, which has been one of the hot research topics during recent years. But the storage stability and the oral bioavailability of catechins are relatively low. Glycosylation is one of the effective ways to improve the stability and bioavailability of catechins to some extent. In order to promote the further study and application of catechins, the glycosidic methods at different sites of catechins were summarized in this paper.

Advances in structural modification of matrine and its analogues / 中草药

Matrine is pyrrolizidine alkaloid derived from Chinese materia medica such as Sophora flavescens and Sophora alopecuroides. It has a wide range of pharmacological effects and abundant resources. Sophocarpine is a D ring 13,14-position dehydrogenation analogue of matrine. Due to the high similarity in structure, sophocarpine also exhibits a wide range of pharmacological activities. However, the pharmacological activities of matrine and sophocarpine are not strong, so a great scale of structural modification were carried out. In this paper, the structural modification and derivative activity of matrine and sophoridine were reviewed according to the modification sites classification, and the future development trend was prospected.

Chemical and pharmacological progress on usnic acid and its derivatives / 中国中药杂志

Usnic acid and its derivatives, a group of organic molecules with great importance, are characteristic to lichens, possessing pharmacological activities such as anti-virus, anti-bacteria, anti-humor, anti-inflammatory, analgesic, and anaesthetic effects. Many of them have been widely used as medicine, but also bring side effects such as dermatitis and liver damages. In the past decades, great efforts by isolation, organic synthesis, and structure modification methods were put on discovery of UA derivatives with higher biological activities or less side effects. This paper describes herein the most progress on natural sources, isolation and structure elucidation, structural characteristics, synthesis and modification results, pharmacological activities and toxicities of UA and its derivatives, hopefully to provide valuable reference for further research.

Research progress on active quercetin derivatives with antitumor effect / 中草药

Quercetin, as a natural product of flavonoids, has many pharmacological activities, and its excellent antitumor activity has been concerned by many scholars at home and abroad in recent years. However, quercetin is poorly water-soluble because of its special molecular structure, which affects its medicinal value in clinic. Therefore, the chemical modification of its structure to improve its bioavailability or antitumor activity has become a hot research topic. In this paper, recent advances in the study of quercetin derivatives with anticancer activity, such as quercetin ester derivatives, metal complexes, ether derivatives, and other derivatives are reviewed, which provides scientific basis for the future development of antitumor drugs from quercetin.

Structural modification and anti-inflammatory biological evaluation of monomeric compounds from Aralia elata / 中草药

Objective: Based on structural modification of monomeric compound calenduloside E from Aralia elata, to evaluate anti-inflammatory activity of the analogues. Methods: Applying oleanolic acid as starting material, the target compounds were prepared by seven steps reactions and evaluated for anti-inflammatory effects by RAW264. 7 cells in vitro. Results: Ten analogues G1-G5 and H1-H5 were synthesized. The structures of the target compounds were identified by spectrum. Pharmacological results showed that all of the compounds had different levels potency of anti-inflammatory effects in cells. In particular, compounds G1-G4 and H1-H3 showed significant anti-inflammatory activity comparing wiht lead compounds. Conclusion: The new compounds G1-G5 and H1-H5 which showed potential of anti-inflammatory biological activity, had not been reported in any literatures and deserved further research.