Triazole tethered C5-curcuminoid-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies

Harbinder Singh, Mandeep Kumar, Kunal Nepali, Manish K. Gupta, Ajit K. Saxena, Sahil Sharma, Preet Mohinder S. Bedi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Keeping in view the confines allied with presently accessible antitumor agents and success of C5-curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C5-curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC50 = 0.82 μM in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin.

Original languageEnglish
Pages (from-to)102-115
Number of pages14
JournalEuropean Journal of Medicinal Chemistry
Volume116
DOIs
Publication statusPublished - Jun 30 2016
Externally publishedYes

Fingerprint

Triazoles
Tubulin
varespladib methyl
Cells
Polymerization
Cytotoxicity
Tumors
Carbon
HCT116 Cells
Cell Line
Curcumin
Structure-Activity Relationship
Tumor Cell Line
Antineoplastic Agents
Inhibitory Concentration 50
Binding Sites
coumarin
Neoplasms

Keywords

  • Antitubulin
  • Antitumor
  • C-curcuminoid
  • Coumarin
  • Docking
  • Hybrid

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Triazole tethered C5-curcuminoid-coumarin based molecular hybrids as novel antitubulin agents : Design, synthesis, biological investigation and docking studies. / Singh, Harbinder; Kumar, Mandeep; Nepali, Kunal; Gupta, Manish K.; Saxena, Ajit K.; Sharma, Sahil; Bedi, Preet Mohinder S.

In: European Journal of Medicinal Chemistry, Vol. 116, 30.06.2016, p. 102-115.

Research output: Contribution to journalArticle

Singh, Harbinder ; Kumar, Mandeep ; Nepali, Kunal ; Gupta, Manish K. ; Saxena, Ajit K. ; Sharma, Sahil ; Bedi, Preet Mohinder S. / Triazole tethered C5-curcuminoid-coumarin based molecular hybrids as novel antitubulin agents : Design, synthesis, biological investigation and docking studies. In: European Journal of Medicinal Chemistry. 2016 ; Vol. 116. pp. 102-115.
@article{07cc5688edfe4efeb0cf0366047fcfde,
title = "Triazole tethered C5-curcuminoid-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies",
abstract = "Keeping in view the confines allied with presently accessible antitumor agents and success of C5-curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C5-curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC50 = 0.82 μM in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin.",
keywords = "Antitubulin, Antitumor, C-curcuminoid, Coumarin, Docking, Hybrid",
author = "Harbinder Singh and Mandeep Kumar and Kunal Nepali and Gupta, {Manish K.} and Saxena, {Ajit K.} and Sahil Sharma and Bedi, {Preet Mohinder S.}",
year = "2016",
month = "6",
day = "30",
doi = "10.1016/j.ejmech.2016.03.050",
language = "English",
volume = "116",
pages = "102--115",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - Triazole tethered C5-curcuminoid-coumarin based molecular hybrids as novel antitubulin agents

T2 - Design, synthesis, biological investigation and docking studies

AU - Singh, Harbinder

AU - Kumar, Mandeep

AU - Nepali, Kunal

AU - Gupta, Manish K.

AU - Saxena, Ajit K.

AU - Sharma, Sahil

AU - Bedi, Preet Mohinder S.

PY - 2016/6/30

Y1 - 2016/6/30

N2 - Keeping in view the confines allied with presently accessible antitumor agents and success of C5-curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C5-curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC50 = 0.82 μM in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin.

AB - Keeping in view the confines allied with presently accessible antitumor agents and success of C5-curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C5-curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC50 = 0.82 μM in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin.

KW - Antitubulin

KW - Antitumor

KW - C-curcuminoid

KW - Coumarin

KW - Docking

KW - Hybrid

UR - http://www.scopus.com/inward/record.url?scp=84962685100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962685100&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2016.03.050

DO - 10.1016/j.ejmech.2016.03.050

M3 - Article

C2 - 27060762

AN - SCOPUS:84962685100

VL - 116

SP - 102

EP - 115

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -