A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study

Nabeel A. Abdul-Rida; Ali M. Farhan; Najim A. Al-Masoudi; Bahjat A. Saeed; Dannah Miller; Ming Fong Lin

doi:10.1007/s11030-020-10038-w

A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study

Nabeel A. Abdul-Rida, Ali M. Farhan, Najim A. Al-Masoudi, Bahjat A. Saeed, Dannah Miller, Ming Fong Lin

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Abstract: New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9–11, oxadiazole, pyrazole and sulfinyl analogs 13–15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity. Graphic abstract: [Figure not available: see fulltext.].

Original language	English (US)
Pages (from-to)	661-671
Number of pages	11
Journal	Molecular Diversity
Volume	25
Issue number	2
DOIs	https://doi.org/10.1007/s11030-020-10038-w
State	Published - May 2021

Keywords

Amides
Anticancer activity
Molecular docking study
Oxadiazole
Pregnene analogs
Pyrazole

ASJC Scopus subject areas

Catalysis
Information Systems
Molecular Biology
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.1007/s11030-020-10038-w

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title = "A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study",

abstract = "Abstract: New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9–11, oxadiazole, pyrazole and sulfinyl analogs 13–15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity. Graphic abstract: [Figure not available: see fulltext.].",

keywords = "Amides, Anticancer activity, Molecular docking study, Oxadiazole, Pregnene analogs, Pyrazole",

author = "Abdul-Rida, {Nabeel A.} and Farhan, {Ali M.} and Al-Masoudi, {Najim A.} and Saeed, {Bahjat A.} and Dannah Miller and Lin, {Ming Fong}",

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year = "2021",

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T2 - synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study

AU - Abdul-Rida, Nabeel A.

AU - Farhan, Ali M.

AU - Al-Masoudi, Najim A.

AU - Saeed, Bahjat A.

AU - Miller, Dannah

AU - Lin, Ming Fong

PY - 2021/5

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N2 - Abstract: New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9–11, oxadiazole, pyrazole and sulfinyl analogs 13–15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity. Graphic abstract: [Figure not available: see fulltext.].

AB - Abstract: New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9–11, oxadiazole, pyrazole and sulfinyl analogs 13–15, via the hydrazide analog 5 of methyl ((5-pregnen-3β,17β-diol-15α-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 μM and 91.8%, and of 79.8% at concentration of 1.0 μM, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity. Graphic abstract: [Figure not available: see fulltext.].

KW - Amides

KW - Anticancer activity

KW - Molecular docking study

KW - Oxadiazole

KW - Pregnene analogs

KW - Pyrazole

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A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study

Abstract

Keywords

ASJC Scopus subject areas

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