New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons

Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ) derivatives, obtained from the natural labdane diterpenoid myrceocommunic acid used as starting material. Different structural modifications, that changed the functionality and stereochemistry of the decalin, have been implemented on the bicyclic core through epoxidation, ozonolysis or decarboxylation, and through induction of biomimetic breaks and rearrangements of the diterpene skeleton. All the isomers generated were completely characterized by spectroscopic procedures. The resulting compounds have been tested in vitro on cultured cancer cells, showing their relevant antineoplastic cytotoxicity, with GI50 values in the μM and sub-μM range. The rearranged compound 8 showed the best cytotoxic results, with GI50 at the submicromolar range, retaining the cytotoxicity level of the parent compounds. In this report, the versatility of the labdane skeleton for chemical transformation and the interest to continue using structural modifications to obtain new bioactive compounds are demonstrated.

Download Full-text

Aurones as New Porcine Pancreatic α-Amylase Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180712150600 ◽

2019 ◽

Vol 16 (3) ◽

pp. 333-340

Author(s):

Khashayar Roshanzamir ◽

Elaheh Kashani-Amin ◽

Azadeh Ebrahim-Habibi ◽

Latifeh Navidpour

Keyword(s):

Biological Activities ◽

Structural Isomers ◽

Structural Requirements ◽

Oh Groups ◽

Structure Activity ◽

Inhibitory Activities ◽

Pharmacological Potential ◽

Relationship Of ◽

Amylase Inhibitors

Background: Aurones, (Z)-2-benzylidenebenzofuran-3-one derivatives, are naturallyoccurring structural isomers of flavones, with promising pharmacological potential. Methods: In this study, the structural requirements for the inhibition of porcine pancreatic α- amylase by hydroxylated or methoxylated aurone derivatives were investigated by assessing their in vitro biological activities against porcine pancreatic α-amylase. Results: The structure-activity relationship of these inhibitors based on both in vitro and in silico findings showed that the hydrogen bonds between the OH groups of the A or B ring of (Z)- benzylidenebenzofuran-3-one derivatives and the catalytic residues of the binding site are crucial for their inhibitory activities. Conclusion: It seems that the OH groups in aurones inhibit α-amylase in a manner similar to that of OH groups in flavones and flavonols.

Download Full-text

Structure-activity relationship of swainsonine. Inhibition of human α-mannosidases by swainsonine analogues

Biochemical Journal ◽

10.1042/bj2590855 ◽

1989 ◽

Vol 259 (3) ◽

pp. 855-861 ◽

Cited By ~ 69

Author(s):

I Cenci di Bello ◽

G Fleet ◽

S K Namgoong ◽

K I Tadano ◽

B Winchester

Keyword(s):

Biological Activities ◽

Human Fibroblasts ◽

Appreciable Effect ◽

Open Chain ◽

Structure Activity ◽

Competitive Inhibitors ◽

Storage Products ◽

Glycoprotein Processing ◽

Relationship Of

The inhibitory properties of a series of synthetic epimers and analogues of swainsonine towards the multiple forms of human alpha-mannosidases were studied in vitro and in cells in culture. Of the five epimers tested, only the 8a-epimer and 8,8a-diepimer of swainsonine were specific and competitive inhibitors (Ki values of 7.5 x 10(-5) and 2 x 10(-6) M respectively) of lysosomal alpha-mannosidases in vitro and induced storage of mannose-rich oligosaccharides in human fibroblasts in culture. The structures of these storage products indicated that processing alpha-mannosidases had also been inhibited. This was consistent with the observed inhibition in vitro of these enzymes by these compounds. In contrast, the 8-epimer, 1,8-diepimer and 2,8a-diepimer of swainsonine had no appreciable effect on any alpha-mannosidases. The corresponding open-chain analogues of swainsonine, namely 1,4-dideoxy-1,4-imino-D-mannitol, of the 8a-epimer, namely 1,4-dideoxy-1,4-imino-D-talitol, and of the 8,8a-diepimer, namely 1,4-dideoxy-1,4-imino-L-allitol, were weaker competitive inhibitors of lysosomal alpha-mannosidase, with Ki values of 1.3 x 10(-5), 1.2 x 10(-4) and 1.2 x 10(-4) M respectively. These analogues also proved less effective at inducing oligosaccharide accumulation and in disturbing glycoprotein processing. These compounds offer the opportunity to determine which alterations in the chirality of the swainsonine molecule affect its inhibitory specificity. A comparison of their biological activities has identified reagents that will be useful for studying steps in the biosynthesis and catabolism of glycoproteins and that may be of potential value in chemotherapy.

Download Full-text

Andrographolide: Synthetic Methods and Biological Activities

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200429100326 ◽

2020 ◽

Vol 20 (16) ◽

pp. 1633-1652

Author(s):

Meng Hao ◽

Min Lv ◽

Hui Xu

Keyword(s):

Antimalarial Activity ◽

Biological Activities ◽

Biological Properties ◽

Hepatoprotective Activity ◽

Synthetic Methods ◽

Antidiabetic Activity ◽

Structural Modifications ◽

Structure Activity ◽

Wide Range ◽

Labdane Diterpenoid

Andrographolide, a labdane diterpenoid, is extracted and isolated from the plants of Andrographis paniculata. Andrographolide and its derivatives exhibited a wide range of biological properties, including anticancer activity, antibacterial activity, hepatoprotective activity, antiinflammatory activity, antiviral activity, antimalarial activity, antidiabetic activity, insecticidal activity, etc. As a continuation, this review aims at giving an overview of the recent advances (from 2015 to 2018) of andrographolide and its derivatives with regard to bioactivities, mechanisms of action, structural modifications, and structure-activity relationships.

Download Full-text

Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study

International Journal of Molecular Sciences ◽

10.3390/ijms22020959 ◽

2021 ◽

Vol 22 (2) ◽

pp. 959

Author(s):

Ruihong Zheng ◽

Shoujie Li ◽

Xuan Zhang ◽

Changqi Zhao

Keyword(s):

Secondary Metabolites ◽

Endophytic Fungi ◽

Biological Activities ◽

Journal Articles ◽

Lead Compounds ◽

Chemical Structures ◽

Structure Activity ◽

Review Study ◽

Relationship Of ◽

New Metabolites

Secondary metabolites isolated from plant endophytic fungi have been getting more and more attention. Some secondary metabolites exhibit high biological activities, hence, they have potential to be used for promising lead compounds in drug discovery. In this review, a total of 134 journal articles (from 2017 to 2019) were reviewed and the chemical structures of 449 new metabolites, including polyketides, terpenoids, steroids and so on, were summarized. Besides, various biological activities and structure-activity relationship of some compounds were aslo described.

Download Full-text

Characterization of Antifungal Secondary Metabolites Produced by Klebsiella pneumoniae and Screening of its Chemical Compounds Using GC-MS

International Journal of Current Pharmaceutical Review and Research ◽

10.25258/ijcprr.v8i02.9198 ◽

2017 ◽

Vol 8 (02) ◽

Author(s):

Abeer Fauzi Al-Rubaye ◽

Mohanad Jawad Kadhim ◽

Imad Hadi Hameed

Keyword(s):

Secondary Metabolites ◽

Klebsiella Pneumoniae ◽

Bioactive Compounds ◽

Methanolic Extract ◽

Biological Activities ◽

Datura Stramonium ◽

Highly Active ◽

Gas Chromatography Mass Spectroscopy ◽

Antibacterial And Antifungal

Bioactives were analyzed using gas chromatography-mass spectroscopy (GC-MS) techniques, then the in vitro antibacterial and antifungal activity of the methanolic extract was evaluated. Twenty two bioactive compounds were identified in the methanolic extract of Klebsiella pneumoniae. GC-MS analysis of Klebsiella pneumoniae revealed the existence of the 6,9,12-Octadecatrienoic acid , phenylmethyl ester , (Z,Z,Z)-, 5,7-Dodecadiyn-1,12-diol, 1,4 Decadiyne, 10,12-Octadecadiynoic acid, 1-Cyclopropyl-3,4-epoxyhex-5-en-1-yne, N,N-Dimethyl-3-methoxy-4-methylphenethylamine, Ethenetricarbonitrile , 3,4-xylidino, Pentyl glycolate, 3-(1,1'-Biphenyl-4-yl)butanenitrile, 4'-Amino-6-methoxyyaurone, Ethanone , 2,2'-(octahydro-2,3-quinoxalinediylidene)bis[1-phe, 1,1'-Bicyclohexyl , 4-methoxy-4'-propyl-, [1.4]Bipiperidinyl-4'-carboxamide , 1'-(chlorobenzenesulfony, 7H-Pyrrolo[2,3-d]pyrimidin-4-amine ,Vinylsulfonamide, 1-Phenyl-2-(4-methylphenyl)diazene 1-oxide, N-Benzyl-N-ethyl-p-isopropylbenzamide, 1-phenyl-2-(4-methylphenyl)-diazene 1-oxide, 1-Benzylindole, Isophthalic acid , di(2-methoxyethyl) ester, 1-Tert , butyl -3,3-bis(trifluoromethyl)diaziridine, 4-Dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene)tyram. Datura stramonium (Alkaloids) was very highly active (6.481±0.24) mm. The results of anti-fungal activity produced by Klebsiella pneumoniae showed that the volatile compounds were highly effective to suppress the growth of Aspergillus flavus (6.287±0.30). Klebsiella pneumoniae produce many important secondary metabolites with high biological activities. Based on the significance of employing bioactive compounds in pharmacy to produce drugs for the treatment of many diseases, the purification of compounds produced by Klebsiella pneumoniae can be useful.

Download Full-text

STRUCTURE-ACTIVITY RELATIONSHIP OF VARIOUS ANALOGUES OF β-CORTICOTRROPHIN DETERMINED BY REFERENCE TO VARIOUS PARAMETERS IN VITRO AND IN VIVO

Acta Endocrinologica ◽

10.1530/acta.0.061s029 ◽

1969 ◽

Vol 61 (1_Suppl) ◽

pp. S29

Author(s):

Pierre A. Desaulles ◽

René Maier ◽

Matthys Staehelin

Keyword(s):

Structure Activity Relationship ◽

Activity Relationship ◽

Structure Activity ◽

Relationship Of

Download Full-text

Synthesis and Antitumor Activity Evaluation of New Phenanthrene-Based Tylophorine Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178615666181025115513 ◽

2019 ◽

Vol 16 (6) ◽

pp. 462-467

Author(s):

Songtao Li ◽

Hongling Zhao ◽

Zhifeng Yin ◽

Shuhua Deng ◽

Yang Gao ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Lines ◽

Antitumor Activities ◽

Human Carcinoma ◽

Carcinoma Cell Lines ◽

Structure Activity ◽

Human Carcinoma Cell ◽

Ic50 Values ◽

Relationship Of

A series of new phenanthrene-based tylophorine derivatives (PBTs) were synthesized in good yield and their structures were characterized by 1H-NMR spectroscopy and ESI MS. In vitro antitumor activity of these compounds against five human carcinoma cell lines, including HCT116 (colorectal), BGC-823 (gastric), HepG-2 (hepatic), Hela (cervical) and H460 (lung) cells, was evaluated by MTT assay. Among these PBTs, compound 6b showed the highest antitumor activities against HCT116 and HepG-2 cell lines with IC50 values of 6.1 and 6.4 μM, respectively, which were comparable to that of adriamycin hydrochloride. The structure-activity relationship of these compounds was also discussed based on the results of their antitumor activity.

Download Full-text

Influence of New Synthetic Xanthones on the Proliferation and Migration Potential of Cancer Cell Lines In Vitro

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190405113519 ◽

2020 ◽

Vol 19 (16) ◽

pp. 1949-1965 ◽

Cited By ~ 1

Author(s):

Natalia Szkaradek ◽

Daniel Sypniewski ◽

Dorota Żelaszczyk ◽

Sabina Gałka ◽

Paulina Borzdziłowska ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Higher Plants ◽

Biological Activities ◽

Human Tumor ◽

Plant Metabolites ◽

Xtt Assay ◽

Treatment Protocols

Background: Natural plant metabolites and their semisynthetic derivatives have been used for years in cancer therapy. Xanthones are oxygenated heterocyclic compounds produced as secondary metabolites by higher plants, fungi or lichens. Xanthone core may serve as a template in the synthesis of many derivatives that have broad biological activities. Objective: This study synthesized a series of 17 new xanthones, and their anticancer potential was also evaluated. Methods: The anticancer potential was evaluated in vitro using a highly invasive T24 cancer cell line. Direct cytotoxic effects of the xanthones were established by IC50 estimation based on XTT assay. Results: 5 compounds of the total 17 showed significant cytotoxicity toward the studied cancer cultures and were submitted to further detailed analysis, including studies examining their influence on gelatinase A and B expression, as well as on the cancer cells migration and adhesion to an extracellular matrix. These analyses were carried out on five human tumor cell lines: A2780 (ovarian cancer), A549 (lung cancer), HeLa (cervical cancer), Hep G2 (liver cancer), and T24 (urinary bladder cancer). All the compounds, especially 4, showed promising anticancer activity: they exhibited significant cytotoxicity towards all the evaluated cell lines, including MCF-7 breast cancer, and hindered migration-motility activity of cancer cells demonstrating more potent activity than α-mangostin which served as a reference xanthone. Conclusion: These results suggest that our xanthone derivatives may be further analyzed in order to include them in cancer treatment protocols.

Download Full-text

Associated microflora of medicinal ferns: biotechnological potentials and possible applications

International Journal of Bioassays ◽

10.21746/ijbio.2016.03.0017 ◽

2016 ◽

Vol 5 (03) ◽

pp. 4927 ◽

Cited By ~ 3

Author(s):

Shubhi Srivastava ◽

Paul A. K.

Keyword(s):

Secondary Metabolites ◽

Growth Promotion ◽

Biological Activities ◽

Hydrolytic Enzymes ◽

In Vitro Production ◽

Wide Range ◽

Negative Effect ◽

Bacteria And Fungi

Plant associated microorganisms that colonize the upper and internal tissues of roots, stems, leaves and flowers of healthy plants without causing any visible harmful or negative effect on their host. Diversity of microbes have been extensively studied in a wide variety of vascular plants and shown to promote plant establishment, growth and development and impart resistance against pathogenic infections. Ferns and their associated microbes have also attracted the attention of the scientific communities as sources of novel bioactive secondary metabolites. The ferns and fern alleles, which are well adapted to diverse environmental conditions, produce various secondary metabolites such as flavonoids, steroids, alkaloids, phenols, triterpenoid compounds, variety of amino acids and fatty acids along with some unique metabolites as adaptive features and are traditionally used for human health and medicine. In this review attention has been focused to prepare a comprehensive account of ethnomedicinal properties of some common ferns and fern alleles. Association of bacteria and fungi in the rhizosphere, phyllosphere and endosphere of these medicinally important ferns and their interaction with the host plant has been emphasized keeping in view their possible biotechnological potentials and applications. The processes of host-microbe interaction leading to establishment and colonization of endophytes are less-well characterized in comparison to rhizospheric and phyllospheric microflora. However, the endophytes are possessing same characteristics as rhizospheric and phyllospheric to stimulate the in vivo synthesis as well as in vitro production of secondary metabolites with a wide range of biological activities such as plant growth promotion by production of phytohormones, siderophores, fixation of nitrogen, and phosphate solubilization. Synthesis of pharmaceutically important products such as anticancer compounds, antioxidants, antimicrobials, antiviral substances and hydrolytic enzymes could be some of the promising areas of research and commercial exploitation.

Download Full-text