Due to genetic and epigenetic mechanisms, cancer have become a resistant disease and there is a need for new molecules having multiple targeting action that promotes apoptosis. Phytomolecules having multiple targeting...Due to genetic and epigenetic mechanisms, cancer have become a resistant disease and there is a need for new molecules having multiple targeting action that promotes apoptosis. Phytomolecules having multiple targeting anticancer activity are in high demand and there is less documentation or information available on these metabolites. It is evident that mushrooms are became the store houses of new anticancer molecules and mushrooms like Agaricus blazei, Antrodia camphorate, Albatrellus confluens, Bolteus badius, Cordyceps militaris, Clitocybe maxima, Funalia trogii, Grifola frondosa, and Inocybe umbrinella, are some of the medicinal mushrooms reported for their cytotoxic activity. Cytotoxic molecules like lentinan, grifolin, illudin-S, psilocybin, ganoderic acid, theanine, and hispolon, have been isolated from various mushroom species. However, studies have been limited only to in vitro cytotoxic mechanisms and very few trials have been conducted to prove the clinical efficacy of these drug leads. Hence, the current review focuses on new anticancer metabolites isolated from various mushrooms having multiple targeting mechanisms in cancer. However, an extensive research is needed to define the biosynthesis and clinical mechanism of these multiple acting metabolites. This review provides a platform for researchers new anticancer drugs and to bring out potent multiple acting anticancer newer drugs.展开更多
Mushrooms are well-known to possess a continuum of anticancer metabolites that are vital in the development of anticancer adjuvant drug leads based on natural products. Owing to the fact that conventional cancer thera...Mushrooms are well-known to possess a continuum of anticancer metabolites that are vital in the development of anticancer adjuvant drug leads based on natural products. Owing to the fact that conventional cancer therapeutic methods were failed to lessen mortality caused by cancer to the estimated level with occurrence of adverse side effects, anticancer agents isolated from natural mushroom sources unarguably make an experimental research area worth mass focus today. The current study was targeted on in vitro cytotoxicity and in silico predictive pharmacological analysis of a flavonoid compound isolated from Fulvifomes fastuosus mushroom. Targeted compound was isolated from the mushroom using different chromatographic methods and identified by NMR spectrometry and mass spectrometry. Cytotoxicity experiments were carried out using MTT assay and apoptotic cells were identified by ethidium bromide/acridine orange staining. The SwissADME tool, BOILED-Egg construction model and Swiss target protein prediction software have been used to perform in silico predictive pharmacological analysis. The isolated compound has been identified as 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione by spectrometric methods. The result of MTT assay showed that 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has potent anticancer activity for hepatoma against Hep-G2 cell line (IC50 = 20.8 μg/ml) being less toxic to normal CC-1 epithelial cells (IC50 = 167.00 μM). The cells treated with compound ex-hibited apoptotic features such as cellular shrinkage, nuclear fragmentation and condensed cytoplasm. In summary, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has shown potent anticancer properties against hepatoma with less cytotoxicity effect on normal cells. Furthermore, in silico study has revealed that properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione may contribute to making a high absorption and clearance of the test compound as not interfering with the therapeutic failure of the compound. The properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo-[3,2-c]pyran-3,2'-furan]-3',4-dione were compatible with well-known anticancer drug lapatinib. In conclusion, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has a high tendency to act as a good anticancer adjuvant drug in the treatment of hepatoma.展开更多
Considerable developments have been observed in fragment-based lead/drug discovery(FBLD/FBDD)recently,with four drugs approved and many others under investigation.Nuclear magnetic resonance(NMR)has gained increasing p...Considerable developments have been observed in fragment-based lead/drug discovery(FBLD/FBDD)recently,with four drugs approved and many others under investigation.Nuclear magnetic resonance(NMR)has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-ligand interactions in a large dynamic range of affinity,from weak hits to highly potent drugs.Here,we summarize NMR applications in fragment-based hit-to-lead evolution,including the construction of a fragment library,screening methods,spectra processing,and the delineation of the protein-ligand binding modes.These state-of-the-art NMR techniques have been exemplified in the discovery of inhibitors against multiple targets over the past five years,and they are expected to continue to provide new insights in the future.展开更多
Tropical diseases such as malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for a large number of deaths annually. Herbs are an excellent source of tropical medicines. Many advancements and discoverie...Tropical diseases such as malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for a large number of deaths annually. Herbs are an excellent source of tropical medicines. Many advancements and discoveries have taken place in the field of drug discovery but still, a major population of tropical diseases relies on herbal traditional medicine. There are some challenges related to policy implementation, efficacy, resistance and toxicity of tropical medicines. There are many tropical diseases such as such as schistosomiasis, leishmaniasis, African sleeping sickness, filariasis and chagas disease which are neglected because very few pharmaceutical companies have shown their interest in developing therapeutics against these diseases of poor people. There are many benefits associated with herbal medicine such as the cost of production, patient tolerance, large scale availability, efficacy, safety, potency, recyclability, and environment friendly. A large number of natural extracts such as curcumin, artemisinin, morphine, reserpine, and hypericin, are in use for treatment of different tropical diseases for a long time. The current review is to discuss the overview of tropical medicinal herbs, its scope and limitations in the modern drug discovery process.展开更多
文摘Due to genetic and epigenetic mechanisms, cancer have become a resistant disease and there is a need for new molecules having multiple targeting action that promotes apoptosis. Phytomolecules having multiple targeting anticancer activity are in high demand and there is less documentation or information available on these metabolites. It is evident that mushrooms are became the store houses of new anticancer molecules and mushrooms like Agaricus blazei, Antrodia camphorate, Albatrellus confluens, Bolteus badius, Cordyceps militaris, Clitocybe maxima, Funalia trogii, Grifola frondosa, and Inocybe umbrinella, are some of the medicinal mushrooms reported for their cytotoxic activity. Cytotoxic molecules like lentinan, grifolin, illudin-S, psilocybin, ganoderic acid, theanine, and hispolon, have been isolated from various mushroom species. However, studies have been limited only to in vitro cytotoxic mechanisms and very few trials have been conducted to prove the clinical efficacy of these drug leads. Hence, the current review focuses on new anticancer metabolites isolated from various mushrooms having multiple targeting mechanisms in cancer. However, an extensive research is needed to define the biosynthesis and clinical mechanism of these multiple acting metabolites. This review provides a platform for researchers new anticancer drugs and to bring out potent multiple acting anticancer newer drugs.
文摘Mushrooms are well-known to possess a continuum of anticancer metabolites that are vital in the development of anticancer adjuvant drug leads based on natural products. Owing to the fact that conventional cancer therapeutic methods were failed to lessen mortality caused by cancer to the estimated level with occurrence of adverse side effects, anticancer agents isolated from natural mushroom sources unarguably make an experimental research area worth mass focus today. The current study was targeted on in vitro cytotoxicity and in silico predictive pharmacological analysis of a flavonoid compound isolated from Fulvifomes fastuosus mushroom. Targeted compound was isolated from the mushroom using different chromatographic methods and identified by NMR spectrometry and mass spectrometry. Cytotoxicity experiments were carried out using MTT assay and apoptotic cells were identified by ethidium bromide/acridine orange staining. The SwissADME tool, BOILED-Egg construction model and Swiss target protein prediction software have been used to perform in silico predictive pharmacological analysis. The isolated compound has been identified as 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione by spectrometric methods. The result of MTT assay showed that 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has potent anticancer activity for hepatoma against Hep-G2 cell line (IC50 = 20.8 μg/ml) being less toxic to normal CC-1 epithelial cells (IC50 = 167.00 μM). The cells treated with compound ex-hibited apoptotic features such as cellular shrinkage, nuclear fragmentation and condensed cytoplasm. In summary, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has shown potent anticancer properties against hepatoma with less cytotoxicity effect on normal cells. Furthermore, in silico study has revealed that properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione may contribute to making a high absorption and clearance of the test compound as not interfering with the therapeutic failure of the compound. The properties of 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo-[3,2-c]pyran-3,2'-furan]-3',4-dione were compatible with well-known anticancer drug lapatinib. In conclusion, 2-(3,4-dihydroxyphenyl)-6-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5'-methylspiro[2H-furo[3,2-c]pyran-3,2'-furan]-3',4-dione has a high tendency to act as a good anticancer adjuvant drug in the treatment of hepatoma.
基金We thank the Ministry of Science and Technology of China(2019YFA0508400 and 2016YFA0500700)the National Natural Science Foundation of China(21874123 and 21807095)Collaborative Innovation Program of Hefei Science Center,CAS(2020HSC-CIP009)for the financial support.
文摘Considerable developments have been observed in fragment-based lead/drug discovery(FBLD/FBDD)recently,with four drugs approved and many others under investigation.Nuclear magnetic resonance(NMR)has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-ligand interactions in a large dynamic range of affinity,from weak hits to highly potent drugs.Here,we summarize NMR applications in fragment-based hit-to-lead evolution,including the construction of a fragment library,screening methods,spectra processing,and the delineation of the protein-ligand binding modes.These state-of-the-art NMR techniques have been exemplified in the discovery of inhibitors against multiple targets over the past five years,and they are expected to continue to provide new insights in the future.
文摘Tropical diseases such as malaria, tuberculosis, trypanosomiasis, and leishmaniasis, account for a large number of deaths annually. Herbs are an excellent source of tropical medicines. Many advancements and discoveries have taken place in the field of drug discovery but still, a major population of tropical diseases relies on herbal traditional medicine. There are some challenges related to policy implementation, efficacy, resistance and toxicity of tropical medicines. There are many tropical diseases such as such as schistosomiasis, leishmaniasis, African sleeping sickness, filariasis and chagas disease which are neglected because very few pharmaceutical companies have shown their interest in developing therapeutics against these diseases of poor people. There are many benefits associated with herbal medicine such as the cost of production, patient tolerance, large scale availability, efficacy, safety, potency, recyclability, and environment friendly. A large number of natural extracts such as curcumin, artemisinin, morphine, reserpine, and hypericin, are in use for treatment of different tropical diseases for a long time. The current review is to discuss the overview of tropical medicinal herbs, its scope and limitations in the modern drug discovery process.
