title: Marine steroids as potential anticancer drug candidates: In silico investigation in search of inhibitors of Bcl-2 and CDK-4/Cyclin D1.
abstract: 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.
authors.affiliation: Natural Products Chemistry Division, CSIR North East Institute of Science & Technology, Jorhat 785006, Assam, India.
authors.forename: Surovi
authors.initials: S
authors.lastname: Saikia
authors.affiliation: Natural Products Chemistry Division, CSIR North East Institute of Science & Technology, Jorhat 785006, Assam, India.
authors.forename: Bhaskor
authors.initials: B
authors.lastname: Kolita
authors.affiliation: Natural Products Chemistry Division, CSIR North East Institute of Science & Technology, Jorhat 785006, Assam, India.
authors.forename: Partha P
authors.initials: PP
authors.lastname: Dutta
authors.affiliation: Natural Products Chemistry Division, CSIR North East Institute of Science & Technology, Jorhat 785006, Assam, India.
authors.forename: Deep J
authors.initials: DJ
authors.lastname: Dutta
authors.affiliation: Natural Products Chemistry Division, CSIR North East Institute of Science & Technology, Jorhat 785006, Assam, India.
authors.lastname: Neipihoi
authors.affiliation: Natural Products Chemistry Division, CSIR North East Institute of Science & Technology, Jorhat 785006, Assam, India.
authors.forename: Shyamalendu
authors.initials: S
authors.lastname: Nath
authors.affiliation: Natural Products Chemistry Division, CSIR North East Institute of Science & Technology, Jorhat 785006, Assam, India. Electronic address: m.j.bordoloi.pub@gmail.com.
authors.forename: Manobjyoti
authors.initials: M
authors.lastname: Bordoloi
authors.affiliation: Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet St., Caugiay, Hanoi, Viet Nam.
authors.forename: Pham Minh
authors.initials: PM
authors.lastname: Quan
authors.affiliation: Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet St., Caugiay, Hanoi, Viet Nam.
authors.forename: Tran Thu
authors.initials: TT
authors.lastname: Thuy
authors.affiliation: Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet St., Caugiay, Hanoi, Viet Nam.
authors.forename: Doan Lan
authors.initials: DL
authors.lastname: Phuong
authors.affiliation: Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet St., Caugiay, Hanoi, Viet Nam.
authors.forename: Pham Quoc
authors.initials: PQ
authors.lastname: Long
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D003198:Computer Simulation; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000737:chemistry; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000737:chemistry; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000737:chemistry; D013215:Starfish / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; C530104:CCND1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D013256:Steroids; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: Anticancer drug candidate; Bcl-2; CDK-4/Cyclin D1; Docking; Echinoderms; Marine steroids