Four New Unusual Pentacyclic Triterpenoids from the Roots of Jasminum sambac (L.) Ait.

Four new unusual pentacyclic triterpenoids (1-4) were isolated from the roots of Jasminum sambac (L.) Ait. Their structures were elucidated by 1D and 2D NMR analysis, single-crystal X-ray diffraction and HRESIMS.

Multifunctional radical-doped polyoxometalate-based host-guest material: photochromism and photocatalytic activity.

An effective strategy to synthesize multifunctional materials is the incorporation of functional organic moieties and metal oxide clusters via self-assembly. A rare multifunctional radical-doped zinc-based host-guest crystalline material was synthesized with a fast-responsive reversible ultraviolet visible light photochromism, photocontrolled tunable luminescence, and highly selective photocatalytic oxidation of benzylic alcohols as a result of blending of distinctively different functional components, naphthalenediimide tectons, and polyoxometalates (POMs). It is highly unique to link π-electron-deficient organic tectons and POMs by unusual POMs anion-π interactions, which are not only conducive to keeping the independence of each component but also effectively promoting the charge transfer or exchange among the components to realize the fast-responsive photochromism, photocontrolled tunable luminescence, and photocatalytic activity.

Synthesis of Rupestonic Acid L-Ephedrine Derivatives with Preliminary In vitro Anti-influenza Viral Activity.

BACKGROUND: Influenza virus is a kind of RNA virus. Nowadays, the high incidence of influenza and the morbidity and mortality of epidemic influenza are substantial. It has been reported that one hundred million people in the world are infected with influenza viruses, and two hundred and fifty thousand to five hundred thousand people die from the flu per year. In 2021, the number of infected persons in China was reported to be 654,700, and 0.07% of the infected persons died. The flu has caused a serious threat to human survival. Although several drugs, such as Zanamivir, Oseltamivir, Peramivir, and Laninamivir, have been used in clinics for the treatment of the influenza virus, there are some shortcomings of these drugs. The strain of influenza H5N1 (avian influenza) has been found to resist the effective drug Oseltamivir. Thus, there is an urgent demand to discover new influenza virus inhibitors to overcome the emergence of influenza antigens. AIMS: This study aimed to develop new influenza virus inhibitors based on the rupestonic acid parent core. OBJECTIVE: The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized in this work for the development of influenza virus inhibitors. METHODS: The target compounds were synthesized using rupestonic acid and L-ephedrine as starting materials. Their structures were characterized by 1H NMR and 13C NMR, and the purity was determined by HPLC. Then, their preliminary in vitro influenza activity was evaluated using Oseltamivir as a reference drug. RESULTS: The results showed that the synthesized rupestonic acid L-ephedrine derivatives A and B were more potent influenza virus inhibitors against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) with the IC50 values of 51.0, 51.0 µM and 441.0, 441.0 µM, respectively, than that of rupestonic acid. By comparing the IC50 of compounds A and B, compound A can be regarded as a very promising lead compound for the development of influenza virus inhibitors. CONCLUSION: The rupestonic acid L-ephedrine ester (A) and rupestonic acid L-ephedrine complex (B) were synthesized and characterized using 1H NMR and 13C NMR. Moreover, their purity was determined by HPLC. Both compounds A and B exhibited more potent activities against the strains of A/PR/8/34 (H1N1) and A/FM/1/47 (H1N1) than rupestonic acid. Compound A can be regarded as a very promising lead compound for the development of influenza virus inhibitors. Based on these results, more rupestonic acid derivatives will be designed and synthesized in the future for the development of influenza virus inhibitors.

The Development History, Structural Composition, and Functions of Influenza Viruses and the Progress of Influenza Virus Inhibitors in Clinics and Clinical Trials.

Flu is an acute respiratory disease caused by influenza viruses. The influenza viruses are classified as Alphainfluenzavirus (influenza A virus, IAV), Betainfluenzavirus (influenza B virus, IBV), Gammainfluenzavirus (influenza C virus, ICV), and Deltainfluenzavirus (influenza D virus, IDV) according to the antigenicity of nucleoproteins (NPs) and matrix (M) proteins in vivo. It is estimated that the seasonal influenza epidemics will cause about 3-5 million cases of serious illness and 290,000-650,000 deaths in the world every year, while influenza A virus is the leading cause of infection and death. Neuraminidase (NA) is one of the most critical targets for the development of anti-influenza virus drugs, and the main drugs clinically applied for the treatment of flu are neuraminidase inhibitors. However, various mutant strains have developed resistance to these inhibitors (For example, the substrains of H274Y in H1N1, H5N1, and E119V in H3N2 have developed resistance to Oseltamivir). Influenza viruses mutate frequently, and new substrains emerge constantly, and the pandemics caused by the new substrains will break out at any time. Therefore, it is urgent to develop new and wide-spectrum influenza virus inhibitors for overcoming the emerging influenza pandemic. Here, we focus on describing the progress of influenza virus inhibitors in clinics and clinical trials to provide a comprehensive reference for the researchers.

Progress of Influenza Viruses and Inhibitors.

Influenza is an acute respiratory disease caused by influenza viruses. It has the characteristics of fast transmission and strong infectivity, and it does great harm to human health and survival. It is estimated that the seasonal influenza epidemics every year will cause about one billion cases of infections and hundreds of thousands of deaths worldwide, while influenza A virus is the leading cause of infection and death. Currently, the main drugs used in clinics to treat influenza viruses are neuraminidase inhibitors, and these drugs have shown excellent efficacy in treating influenza viruses. However, various mutant strains have developed resistance to these effective drugs in clinics (such as the subtype mutant strains of H274Y in H1N1 or H5N1 and E119V in H3N2 have developed resistance to Oseltamivir). Influenza viruses mutate frequently, and new viral strains are constantly discovered, and the pandemics will break out at any time. Therefore, it is urgent to develop efficient and broad-spectrum drugs to prevent and treat the influenza pandemic caused by the emerging new subtypes. This review focuses on describing the pandemic history, the structure, function and prevention methods of influenza viruses and the progress of the development of anti-influenza drugs, to provide the reference for prevention and treatment of influenza viruses and development of influenza virus inhibitors.

A Review on Shikonin and Its Derivatives as Potent Anticancer Agents Targeted against Topoisomerases.

The topoisomerases (TOPO) play indispensable roles in DNA metabolism, by regulating the topological state of DNA. Topoisomerase I and II are the well-established drug-targets for the development of anticancer agents and antibiotics. These drugs-targeting enzymes have been used to establish the relationship between drug-stimulated DNA cleavable complex formation and cytotoxicity. Some anticancer drugs (such as camptothecin, anthracyclines, mitoxantrone) are also widely used as Topo I and Topo II inhibitors, but the poor water solubility, myeloma suppression, dose-dependent cardiotoxicity, and multidrug resistance (MDR) limited their prolong use as therapeutics. Also, most of these agents displayed selective inhibition only against Topo I or II. In recent years, researchers focus on the design and synthesis of the dual Topo I and II inhibitors, or the discovery of the dual Topo I and II inhibitors from natural products. Shikonin (a natural compound with anthraquinone skeleton, isolated from the roots of Lithospermum erythrorhizon) has drawn much attention due to its wide spectrum of anticancer activities, especially due to its dual Topo inhibitive performance, and without the adverse side effects, and different kinds of shikonin derivatives have been synthesized as TOPO inhibitors for the development of anticancer agents. In this review, the progress of the shikonin and its derivatives together with their anticancer activities, anticancer mechanism, and their structure-activity relationship (SAR) was comprehensively summarized by searching the CNKI, PubMed, Web of Science, Scopus, and Google Scholar databases.

Isolation, Structural Elucidation of a New Triterpenoid from the Roots of Jasminum sambac (L.) Ait. with Potent Cytotoxicity against MCF-7 Cell Lines.

A new triterpenoid was isolated from the roots of Jasminum sambac (L.) Ait. Its structure was elucidated by 1D and 2D NMR analysis, single crystal X-ray diffraction, and HRESIMS. This compound exhibited potent in vitro anticancer efficacy against MCF-7 cell lines with IC50's of 193.5 µM for 24 h and 154.6 µM for 48 h.

Chemical Constituents from the Roots of Jasminum sambac (L.) Ait. and their Cytotoxicity to the Cancer Cell Lines.

BACKGROUND: The roots of J. sambac is the Traditional Chinese Medicine (TCM) with analgesic and anesthetic effects. However, relatively fewer studies on the chemical compositions and the biological activities of the roots of J. sambac have been carried out till now. We studied the chemical compositions of the roots of J. sambac planted in Fujian Province to discover new compounds from this TCM to develop new drugs or drug candidates. AIM: This work aims to find the new compounds from the roots of Jasminum sambac (L.) Ait. (J. sambac) for the development of new drugs or drug candidates. METHODS: The dichloromethane (DCM) extract was selected to isolate over silica gel column chromatography to obtain different polar fractions. Several similar fractions were combined according to Thin Layer Chemotherapy (TLC) or High-Performance Liquid Chromatography (HPLC) analysis. The combined fractions were reisolated by silica gel column chromatography, preparative TLC or HPLC to obtain nine pure compounds (1-9). The purity of the isolated compounds was detected by HPLC, and their structures were determined by 1D, 2D NMR, and HRESIMS analysis. The in vitro anticancer activity was evaluated using Cell Counting Kit-8 (CCK8) method. RESULTS: Nine compounds were isolated in this work. Compounds (1-3) are new compounds, while compounds (4-9) were isolated for the first time from the roots of J. sambac. Their structures were elucidated by 1D, 2D NMR, and HRESIMS analysis. The biological evaluation showed that compound 7 exhibited potent cytotoxic efficacy against MCF-7 cell lines with IC50 values of 148.3 µM for 24 hs and 35.94 µM for 48 hs, respectively; compound 1 displayed significant cytotoxic potential against MCF-7 cell lines with IC50 value of 38.5 µM for 24 hs; while compound 3 and 4 displayed potent cytotoxic effects against MCF-7 cell lines with IC50 values of 161.1 µM and 243.7 µM for 48 hs, respectively. CONCLUSION: We discovered new compounds from the roots of J. sambac. and several compounds exhibited potent cytotoxity to MCF-7 cell lines. This work encourages us to further study the chemical constituents and their biological activities from the roots of J. sambac.

New neo-Clerodane Diterpenoids Isolated from Ajuga decumbens Thunb., Planted at Pingtan Island of Fujian Province with the Potent Anticancer Activity.

AIMS: The aim of this study is to find the anticancer lead compounds or drug candidates from Chinese Traditional Plant Medicine of Ajuga decumbens Thunb. BACKGROUND: Ajuga decumbens Thunb. has been used in clinical for a long time in China and was selected in "Chinses Pharmacopoeia" (part I in 1977) for its wide spectrum biological activities: such as anticancer, antioxidant, antifeedant, antibacterial, anti-inflammatory, antihyperlipidemic, anti-cholinesterase and cytotoxicity activities. However, there are relatively fewer studies of Ajuga decumbens Thunb. that have been carried out till now. For some years, our research group focused on the discovery of new anticancer agents, so we studied the chemical compositions of Ajuga decumbens Thunb., planted in Pingtan island of Fujian Province, to discover new anticancer lead compounds or candidates from this Chinese Traditional Plant Medicine. METHODS: The dichloromethane (DCM) extract was obtained in this work, and then this extract was used for silica gel column chromatography to obtain different polar fractions. Several similar fractions were combined according to TLC or HPLC analysis. The combined fractions were isolated by preparative TLC or preparative HPLC to obtain the pure compounds and HPLC was used to detect the purity. All isolated compounds were determined by NMR (1HNMR, 13CNMR, DEPT, HMBC, HSQC, 1H-1H COSY and NOESY), HRESIMS and single crystal X-ray diffraction methods. The in vitro anticancer activity was evaluated using CCK8 method. RESULTS: Seven compounds [three new compounds 1-3; and four known compounds (Ajugacumbins A, Ajugacumbin B, Ajugamarin A2 and Ajugamarin A1)] were isolated from Ajuga decumbens Thunb. in this work, and their structures were confirmed. The biological evaluation showed that 3 and Ajugamarin A1 exhibited potent in vitro anticancer activity both against A549 cell lines with IC50s=71.4 µM and 76.7 µM; and against Hela cell lines with IC50s=71.6 mM and 5.39×10-7 µM, respectively. CONCLUSION: Compounds (3 and Ajugamarin A1) can be regarded as the lead compounds for the development of anticancer agents.

An Overview of Dihydroartemisinin as a Promising Lead Compound for Development of Anticancer Agents.

Dihydroartemisinin (DHA) is a derivative of artemisinin, which firstly showed higher antimalarial activity. Over the years, DHA has also been discovered to exhibit higher anticancer efficacy without adverse side effects. Although some shortcomings have been discovered during biological evaluation (such as poor aqueous solubility, short half-life, and initial burst release effect), several attempts have been developed to overcome these shortcomings. For example, appropriate delivery techniques were used to improve its anticancer efficacy. In this minireview, we focused on summarizing the anticancer mechanisms, anticancer efficacy of free DHA and in combination therapies, hybrids, and nanoparticle formulations, which will provide adequate insights for its clinical use as anticancer agents, and on the design and synthesis of DHA derivatives for the development of anticancer agents.

Isolation, structural elucidation of new phytoecdysteroids from Ajuga decumbens Thunb.

Five new phytoecdysteroids (1, 2, 3, 4, and 5) were isolated from Ajuga decumbens Thunb. planted at Pingtan island of Fujian Province. Their structures were elucidated by NMR(1H NMR, 13C NMR, DEPT, HMBC, HSQC, 1H-1H COSY, ROESY), and HRESIMS. Especially, compound 2 is the epimer of Cyasterone, which was directly confirmed using single crystal X-ray diffraction analysis.

New Ferrocene Formates Bearing Isoxazole Moieties: Synthesis, Characterization, X-ray Crystallography, and Preliminarily Cytotoxicity against A549, HCT116, and MCF-7 Cell Lines.

AIMS: To develop new anticancer agents based on ferrocene core. BACKGROUND: Cancer has become the major cause of human death globally. The death caused by cancer mainly focuses on lung cancer, breast cancer, liver cancer, carcinoma of the colon, and rectum. Some small molecular inhibitors have been authorized by FDA for the treatment of cancer and several candidates are in different phases of clinical trials. However, cancer chemotherapy is still highly inadequate. Thus, it is indispensable to develop novel anticancer agents. OBJECTIVE: Based on the previous good results, twelve novel structures of ferrocene formates bearing isoxazole moiety (3a-3l) were synthesized in this work for the development of anticancer agents. METHODS: The target compounds were synthesized using Ferrocenecarboxylic acid and 3-[(R)-substitutedphenyl]- isoxazole-5-methanol catalyzed by DCC and DMAP. The structures of target compounds were characterized by 1H NMR, 13C NMR, MS, HR-MS and XRD. Then, their preliminarily in vitro cytotoxicity against A549, HCT116, and MCF-7 cell lines was evaluated using the MTT method. RESULTS: The results showed that most compounds exhibited moderate cytotoxicity against A549, HCT116, and MCF-7 cell lines compared with the positive control gefitinib. However, (3b, 3c, 3e, 3j, and 3k) simultaneously exhibited stronger inhibitory activity against A549, HCT116, and MCF-7 cell lines, which can be regarded as promising metal-based lead compounds for the development of anticancer agents. CONCLUSION: In this work, twelve new structures of ferrocene derivatives containing isozaole moiety were synthesized and their cytotoxicity against 549, HCT116, and MCF-7 cell lines was evaluated. (3b, 3c, 3e, 3j, and 3k) simultaneously exhibited stronger inhibitory activity towards A549, HCT116, and MCF-7 cell lines, which can be regarded as promising metal-based lead compounds for the development of anticancer agents.

(Z)-N-[3-(4-Bromo-benzo-yl)-1,3-thia-zolidin-2-yl-idene]cyanamide.

In the title compound, C(11)H(8)BrN(3)OS, the dihedral angle between the benzene and thia-zolidine rings is 63.4 (2)°. Inter-molecular C-H⋯N inter-actions help to stabilize the crystal structure.

The Progress of the Anticancer Agents Related to the Microtubules Target.

Anticancer drugs based on the microtubules target are potent mitotic spindle poison agents, which interact directly with the microtubules, and were classified as microtubule-stabilizing agents and microtubule-destabilizing agents. Researchers have worked tremendously towards the improvements of anticancer drugs, in terms of improving the efficacy, solubility and reducing the side effects, which brought about advancement in chemotherapy. In this review, we focused on describing the discovery, structures and functions of the microtubules as well as the progress of anticancer agents related to the microtubules, which will provide adequate references for researchers.

(E)-1-(1H-Benzotriazol-1-yl 3-oxide)-3-methoxy-but-2-en-1-one.

The title compound, C(11)H(11)N(3)O(3), crystallizes with two independent mol-ecules of similar geometry in the asymmetric unit. The mol-ecular conformations are stabilized by intra-molecular C-H⋯O hydrogen bonds. The crystal packing consists of wave-like layers parallel to the bc plane formed by inter-molecular C-H⋯O hydrogen-bonding inter-actions involving only one independent mol-ecule.

(5R,8R)-2-(3,8-Dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octa-hydro-azulen-5-yl)acrylic acid (rupestonic acid).

The title compound, C(15)H(20)O(3), crystallizes with two independent mol-ecules in the asymmetric unit. In both mol-ecules, the seven-membered ring adopts a chair conformation. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into chains extending in the [201] direction. The absolute configuration was assigned on the basis of the starting materials.

7-Nitro-quinazolin-4(3H)-one.

In the crystal structure of the title compound, C(8)H(5)N(3)O(3), inter-molecular N-H⋯O hydrogen bonds link mol-ecules into centrosymmetric dimers. These dimers are, in turn, linked though weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds and π-π stacking inter-actions, with centroid-centroid distances of 3.678 (3) Å, into a three-dimensional network.

Synthesis, Structural Characterization of a Novel Ferrocene Derivative and Preliminarily Anticancer Activity.

A novel structure of ferrocene derivative 1 was synthesized with cyanuric chloride and ferrocenemethanol as starting materials. The synthesized compound was fully characterized using 1H NMR, 13C NMR, MS and XRD. Subsequently, the in vitro anticancer effect against A549, HCT116 and MCF-7 cell lines was preliminarily evaluated by the MTT method. The result showed that this compound exhibits good cytotoxic effect on A549, HCT116 and MCF-7 cell lines.

Synthesis and Biological Evaluation of Quinazoline Derivatives as Potential Anticancer Agents (II).

Under the guidance of our previous work, we synthesized 21 new structures of quinazolines (3a~3u) and evaluated their in vitro anticancer activity against A549, HCT116 and MCF-7 cell lines using the MTT method. Most compounds showed good to excellent anticancer activity. In particular, 3o (regarded as erlotinib analogues) has marked anticancer activity against A549, HCT116 and MCF-7 cell lines (IC50s: 4.26, 3.92 and 0.14 µM, respectively) as compared with the standard anticancer drug gefitinib (IC50s: 17.9, 21.55 and 20.68 µM, respectively), and which can be regarded as the best candidate for development of anticancer drugs.

Anticancer Advances of Matrine and Its Derivatives.

As the second leading cause of death in the world, the total number caused by cancer in 2008 is 1.4 million. The great cancer incidence worldwide increases the search for new, safer and efficient anticancer agents (especially to find the new structures and more active anticancer drugs from the natural products) aiming the prevention or the cure of such illness. For a century, matrine (an alkaloid isolated from sophorae flavescens Ait.) has been widely studied in the field of cancer. This review briefly describes the progress of matrine, its derivatives and their anticancer activity.