Marine steroids as potential anticancer drug candidates: In silico investigation in search of inhibitors of Bcl-2 and CDK-4/Cyclin D1

• Published in: Steroids Vol. 102; pp. 7 - 16
• Main Authors: Saikia, Surovi, Kolita, Bhaskor, Dutta, Partha P., Dutta, Deep J., Neipihoi, Nath, Shyamalendu, Bordoloi, Manobjyoti, Quan, Pham Minh, Thuy, Tran Thu, Phuong, Doan Lan, Long, Pham Quoc
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2015
• Subjects: Animals; Anticancer drug candidate; Antineoplastic Agents - chemistry; Bcl-2; CDK-4/Cyclin D1; Computer Simulation; Cyclin D1 - antagonists & inhibitors; Cyclin D1 - chemistry; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 4 - chemistry; Docking; Echinoderms; Humans; Marine steroids; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - chemistry; Starfish - chemistry; Steroids - chemistry; Bcl-2; Docking; CDK-4/Cyclin D1; Anticancer drug candidate; Echinoderms; Marine steroids
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2015.06.012

•In silico screening of star fish steroids against Bcl-2 and CDK-4/Cyclin D1.•Their physico-chemical, drug-likeliness and ADMET properties were determined.•Their binding affinity with Bcl-2 and CDK-4/Cyclin D1 were determined.•Two steroids have excellent potential against various cancer types.
Star fishes (Asteroidea) are rich in polar steroids with diverse structural characteristics. The structural modifications of star fish steroids occur at 3β, 4β, 5α, 6α (or β), 7α (or β), 8, 15α (or β) and 16β positions of the steroidal nucleus and in the side chain. Widely found polar steroids in starfishes include polyhydroxysteroids, steroidal sulfates, glycosides, steroid oligoglycosides etc. Bioactivity of these steroids is less studied; only a few reports like antibacterial, cytotoxic activity etc. are available. In continuation of our search for bioactive molecules from natural sources, we undertook in silico screening of steroids from star fishes against Bcl-2 and CDK-4/Cyclin D1 – two important targets of progression and proliferation of cancer cells. We have screened 182 natural steroids from star fishes occurring in different parts of the world and their 282 soft-derivatives by in silico methods. Their physico-chemical properties, drug-likeliness, binding potential with the selected targets, ADMET (absorption, distribution, metabolism, toxicity) were predicted. Further, the results were compared with those of existing steroidal and non steroidal drugs and inhibitors of Bcl-2 and CDK-4/Cyclin D1. The results are promising and unveil that some of these steroids can be potent leads for cancer treatments.