Isoquinoline Alkaloids and Their Analogs: Nucleic Acid and Protein Binding Aspects, and Therapeutic Potential for Drug Design

Kumar, Gopinatha Suresh

doi:10.1002/9783527684403.ch9

Cited by 4 publications

(1 citation statement)

References 129 publications

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“…The use of alkaloids as medicine by humans date back thousands of years and the most important of them includes morphine, quinine, taxol, camptothecin, and berberine. Besides other pharmacological importance, plant alkaloids have been found to be potent anti-cancer agent targeting deoxyribonucleic acids [2][3][4][5][6]. Beta carboline alkaloids are one of such plant alkaloids, which have proven to be highly cytotoxic with several biological and nucleic acid binding effects [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of harmaline, a novel alkaloid, against cervical cancer cells in vitro: Apoptotic induction and DNA interaction study

2018

J App Biol Biotech

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The study emphasizes the growth inhibitory effect of harmaline on HeLa (human cervical cancer) cell line and mode and mechanism of binding with CT DNA (calf thymus DNA). The results of cytotoxic study performed through MTT assay indicates that harmaline have concentration dependent growth inhibitory effect on HeLa cell line with GI 50 value of 28 µM. Furthermore, the alkaloid induced DNA damage and changes in mitochondrial membrane potential in the cell line. The alkaloid shows reactive oxygen species dependent cellular damage with significant arrest in G 2 /M population of the cell. Biophysical experiments further established the K i w value (product of cooperative binding affinity and the cooperative factor) of harmaline with CT DNA to be 5.60 × 10 5 M −1. Harmaline showed a progressive quenching of the fluorescence emission spectra. Circular dichroism study shows significant structural changes of DNAwith subsequent induction of optical activity in the bound achiral alkaloid molecule. The alkaloid stabilizes the DNA to 10°C. Intercalated state of harmaline inside DNA helix was shown by viscometric and ferrocyanide quenching. The results highlight the importance of alkaloid-DNA interaction for developing nucleic acid based therapeutic agents.

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