Novel class of hybrid natural products as antidiabetic agents

Raj, Kanwal; Misra, Namita; Pachauri, G; Sharma, Monika; Tamrakar, Akhilesh K.; Singh, Amar; Srivastava, Arvind K.; Kamireddy, Kiran; Rao, C. V. N.; Prubhu, S.R.

doi:10.1080/14786410701824940

Cited by 10 publications

(3 citation statements)

References 21 publications

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“…against gonorrhea, rheumatism, jaundice, boils, scabies, bruising and dysmenorrhea 12–14. Previous studies demonstrated that many xanthones exert varied pharmacological effects, including antimicrobial,13, 15 antioxidant,15 antidiabetic,16 anti‐inflammatory17 and hepatoprotective activities 18. Besides the above functions, the interesting structural scaffold and the anticancer potential of xanthones have drawn more and more attention 19.…”

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confidence: 99%

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

Wang

Kuang

Pan

et al. 2010

Intl Journal of Cancer

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Isoalvaxanthone (IAX) is a bioactive xanthone isolated from Cudrania cochinchinensis (Lour.). However, the function and mechanism of this compound in cancer migration and invasion have not been elucidated to date. In this study, we found that IAX could suppress various steps of tumor metastasis including proliferation, migration and invasion in a dose-dependent manner on colorectal cancer cells. Especially matrix metalloproteinase 2 (MMP-2), the pivotal factor in cancer invasion, was suppressed both on activation and expression after treated with IAX. To understand the underlying mechanism of IAX on the inhibitory effect of proliferation, migration and invasion, we demonstrated that IAX could significantly inhibit the activation of Rac1 but has undetectable effect on GTP-RhoA, GTP-Cdc42 and the phosphorylation of ERK1/2, p38 MAPK and JNK. Moreover, IAX showed little influence on the transcriptional activity of nuclear transcription factor jB (NF-jB) but strongly inhibited that of activator protein-1 (AP-1), which is the downstream transcriptional factor of Rac1. Together, our results indicate that IAX exerts anticancer effect in SW620 cells by targeting MMP-2 via regulating the activity of Rac1 and AP-1. These results are the first to reveal the function of IAX in tumor metastasis and its underlying molecular mechanism, thus suggest IAX to be a promising antimetastatic agent.Colorectal carcinoma is the third most common form of cancer and the second leading cause of morbidity and mortality in the world.1 Metastasis, a main cause of death in cancer patients, contributes to the high mortality of colorectal cancer, despite most early stage colorectal cancer is curable with surgical resection. In metastasis, malignant tumor cells moved from the primary tumor to a secondary distant organ through a complex multistage process involving the coordination of several signaling pathways that allow changes in cell morphology, migration and invasion.2,3 During the process of metastasis, degradation of the extracellular matrix (ECM) by proteases such as matrix metalloproteinases (MMPs) is important. MMP-2 (gelatinase A) and MMP-9 (gelatinase B) are the most vital proteases for the degradation of the main constituent of the basement membrane, type IV collagen and are, therefore, pivotal for cancer invasion and metastasis. 4 The Rho family proteins (RhoA, Rac1 and Cdc42) are small GTP-binding proteins with a distinct function in cell survival, cytoskeleton organization, adhesion and motility, thus become important targets of cancer chemotherapy. 5,6 It is now known that these biological activities are coordinated by the concerted action of different Rho/Rac subfamily members. For instance, RhoA function is required for the initial formation of the lamellipodia and the establishment of focal adhesions and stress fibers, Rac1 promotes membrane ruffles and lamellipodia and Cdc42 trigger filopodia in the leading edge of migrating cells.7 Small GTPases are also molecular switches that trigger signaling cascades in response to upstrea...

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confidence: 99%

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

Wang

Kuang

Pan

et al. 2010

Intl Journal of Cancer

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“…Inhibitory effect of synthetic xanthones 230e235 on a-glucosidase activity a b [84]. b Percentage of inhibition at the highest tested concentration (100 mM).…”

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confidence: 99%

A comprehensive review on xanthone derivatives as α-glucosidase inhibitors

Santos

Freitas

Fernandes

2018

European Journal of Medicinal Chemistry

148

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a-Glucosidase plays an important role in carbohydrate metabolism and is therefore an attractive therapeutic target for the treatment of diabetes, obesity and other related complications. In the last two decades, considerable interest has been given to natural and synthetic xanthone derivatives in this field of research. Herein, a comprehensive review of the literature on xanthones as inhibitors of a-glucosidase activity, their mechanism of action, experimental procedures and structure-activity relationships have been reviewed for more than 280 analogs. With this overview we intend to motivate and challenge researchers (e.g. chemistry, biology, pharmaceutical and medicinal areas) for the design of novel xanthones as multipotent drugs and exploit the properties of this class of compounds in the management of diabetic complications.

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“…[1][2][3] Carbazole and its derivative have attributed promising biological activities such as anti-inflammatory, 4 antitumor, anti-diabetic, 5 anti-oxidant, 6 anti-tubercular, anti-bacterial, 7 anti-fungal, 8 and anti-histaminic activity. 9 According to Drissa new carbazole alkaloids named calothrixins from cell extracts of cyanobacterial Calothrix species. They showed a unique indolo [3, 2-j] phenanthridine ring system, in antiplasmodial and anticancer assays at nanomolar concentrations it exerts in vitro growth inhibitory.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Biological Screening of Novel Carbazole Tethered Oxyethylamino Derivatives as Antimicrobial Agent

Sabale,

Sayyad B,

2023

Ind. J. Pharm. Edu. Res

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Background: Carbazole is an important scaffold known to be associated with several biological activities including antimicrobial activities. Incorporation 4-oxothiazolidine moiety in carbazole moiety may lead to a new series of antimicrobials compounds. Aim: In this study, design and synthesis of novel carbazole tethered oxyethylamino was started with carbazole as basic pharmacophore and evaluated for antimicrobial activity. Materials and Methods: Molecular docking of carbazole derivatives was carried out by Schrödinger (Maestro 10.5v) active compound were Synthesized and screened for in vitro antimicrobial activity against Candida albicans and gram-positive and gram-negative bacterial strains such as Staphylococcus aureus, Bacillus subtilis, E. coli. MIC was calculated by standard agar tube dilution method. Results: All Compounds shown good antimicrobial activity at 25 (µg/ml) -510 (µg/ml). The molecular docking studies demonstrated ligand protein interaction. Conclusion: carbazole represent novel set of lead for the designing of novel antimicrobial agents.

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Novel class of hybrid natural products as antidiabetic agents

Cited by 10 publications

References 21 publications

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

Isoalvaxanthone inhibits colon cancer cell proliferation, migration and invasion through inactivating Rac1 and AP‐1

A comprehensive review on xanthone derivatives as α-glucosidase inhibitors

Design, Synthesis and Biological Screening of Novel Carbazole Tethered Oxyethylamino Derivatives as Antimicrobial Agent

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