Synthesis and biological evaluation of triazole-vanillin molecular hybrids as anti-cancer agents

Gangavaram V.M. Sharma, Kandikonda S. Kumar, Sheri V. Reddy, Arumugam Nagalingam, Kathleen M. Cunningham, Ramesh Ummanni, Helmut Hugel, Dipali Sharma, Sanjay V. Malhotra

Research output: Contribution to journalArticle

Abstract

Background: Triazole based drugs are widely used in cancer patients for the treatment of life-threatening invasive fungal infections. A recent report on the usefulness of 1,2, 3- triazole scaffold for the inhibition of tyrosine kinases stimulated our curiosity to design new molecules based on this moiety. Methods: A series of new heterocyclic compounds containing 1,2,3 triazole moiety tethered to substituted vanillin or isovanillin were synthesized and analysed for their anticancer activity. The cyclopen-tyl/cyclohexyl ethers derived from vanillin and isovanillin were subsequently treated with MeMgI to give the carbinols. Reaction of these carbinols with TMSN3 and ZrCl4 as Lewis acid gave the desired azides. Click chemistry on azides with diverse acetylenes furnished the triazoles. The new triazole hybribs were screened o against 60 human cancer cell lines at a 10μM dose for their potential anticancer activity. Results: The two active compounds (8a, 10a) showed strong inhibitory effect against different cell lines, with highest inhibition against breast cancer panel. To elucidate the underlying molecular mechanisms, these compounds were examined for their clonogenic potential and anchorage-independent growth of estrogen receptor positive (MCF7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-468) breast cancer cells and investigated for induction apoptotic pathways. Conclusion: The outcomes from the current study will add much to the existing knowledge of the breast cancer research. This provides a rewarding conclusion and opens the way for future researchers to design and synthesize the novel active compounds against breast cancer.

Original languageEnglish (US)
Pages (from-to)223-235
Number of pages13
JournalCurrent Bioactive Compounds
Volume13
Issue number3
DOIs
StatePublished - Sep 1 2017

Fingerprint

Triazoles
Breast Neoplasms
Azides
Neoplasms
Estrogen Receptors
Methanol
Click Chemistry
Heterocyclic Compounds
Cell Line
Lewis Acids
Exploratory Behavior
Alkynes
Ethers
Protein-Tyrosine Kinases
Research Personnel
Outcome Assessment (Health Care)
vanillin
Growth
Research
Pharmaceutical Preparations

Keywords

  • Anticancer
  • Apoptosis
  • Breast cancer
  • Cancer therapy
  • Molecular hybrids
  • Triazole-vanillin

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Sharma, G. V. M., Kumar, K. S., Reddy, S. V., Nagalingam, A., Cunningham, K. M., Ummanni, R., ... Malhotra, S. V. (2017). Synthesis and biological evaluation of triazole-vanillin molecular hybrids as anti-cancer agents. Current Bioactive Compounds, 13(3), 223-235. https://doi.org/10.2174/1573407213666161128121435

Synthesis and biological evaluation of triazole-vanillin molecular hybrids as anti-cancer agents. / Sharma, Gangavaram V.M.; Kumar, Kandikonda S.; Reddy, Sheri V.; Nagalingam, Arumugam; Cunningham, Kathleen M.; Ummanni, Ramesh; Hugel, Helmut; Sharma, Dipali; Malhotra, Sanjay V.

In: Current Bioactive Compounds, Vol. 13, No. 3, 01.09.2017, p. 223-235.

Research output: Contribution to journalArticle

Sharma, Gangavaram V.M. ; Kumar, Kandikonda S. ; Reddy, Sheri V. ; Nagalingam, Arumugam ; Cunningham, Kathleen M. ; Ummanni, Ramesh ; Hugel, Helmut ; Sharma, Dipali ; Malhotra, Sanjay V. / Synthesis and biological evaluation of triazole-vanillin molecular hybrids as anti-cancer agents. In: Current Bioactive Compounds. 2017 ; Vol. 13, No. 3. pp. 223-235.
@article{a72a5e9b297b4784a57367c0434a83a8,
title = "Synthesis and biological evaluation of triazole-vanillin molecular hybrids as anti-cancer agents",
abstract = "Background: Triazole based drugs are widely used in cancer patients for the treatment of life-threatening invasive fungal infections. A recent report on the usefulness of 1,2, 3- triazole scaffold for the inhibition of tyrosine kinases stimulated our curiosity to design new molecules based on this moiety. Methods: A series of new heterocyclic compounds containing 1,2,3 triazole moiety tethered to substituted vanillin or isovanillin were synthesized and analysed for their anticancer activity. The cyclopen-tyl/cyclohexyl ethers derived from vanillin and isovanillin were subsequently treated with MeMgI to give the carbinols. Reaction of these carbinols with TMSN3 and ZrCl4 as Lewis acid gave the desired azides. Click chemistry on azides with diverse acetylenes furnished the triazoles. The new triazole hybribs were screened o against 60 human cancer cell lines at a 10μM dose for their potential anticancer activity. Results: The two active compounds (8a, 10a) showed strong inhibitory effect against different cell lines, with highest inhibition against breast cancer panel. To elucidate the underlying molecular mechanisms, these compounds were examined for their clonogenic potential and anchorage-independent growth of estrogen receptor positive (MCF7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-468) breast cancer cells and investigated for induction apoptotic pathways. Conclusion: The outcomes from the current study will add much to the existing knowledge of the breast cancer research. This provides a rewarding conclusion and opens the way for future researchers to design and synthesize the novel active compounds against breast cancer.",
keywords = "Anticancer, Apoptosis, Breast cancer, Cancer therapy, Molecular hybrids, Triazole-vanillin",
author = "Sharma, {Gangavaram V.M.} and Kumar, {Kandikonda S.} and Reddy, {Sheri V.} and Arumugam Nagalingam and Cunningham, {Kathleen M.} and Ramesh Ummanni and Helmut Hugel and Dipali Sharma and Malhotra, {Sanjay V.}",
year = "2017",
month = "9",
day = "1",
doi = "10.2174/1573407213666161128121435",
language = "English (US)",
volume = "13",
pages = "223--235",
journal = "Current Bioactive Compounds",
issn = "1573-4072",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - Synthesis and biological evaluation of triazole-vanillin molecular hybrids as anti-cancer agents

AU - Sharma, Gangavaram V.M.

AU - Kumar, Kandikonda S.

AU - Reddy, Sheri V.

AU - Nagalingam, Arumugam

AU - Cunningham, Kathleen M.

AU - Ummanni, Ramesh

AU - Hugel, Helmut

AU - Sharma, Dipali

AU - Malhotra, Sanjay V.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background: Triazole based drugs are widely used in cancer patients for the treatment of life-threatening invasive fungal infections. A recent report on the usefulness of 1,2, 3- triazole scaffold for the inhibition of tyrosine kinases stimulated our curiosity to design new molecules based on this moiety. Methods: A series of new heterocyclic compounds containing 1,2,3 triazole moiety tethered to substituted vanillin or isovanillin were synthesized and analysed for their anticancer activity. The cyclopen-tyl/cyclohexyl ethers derived from vanillin and isovanillin were subsequently treated with MeMgI to give the carbinols. Reaction of these carbinols with TMSN3 and ZrCl4 as Lewis acid gave the desired azides. Click chemistry on azides with diverse acetylenes furnished the triazoles. The new triazole hybribs were screened o against 60 human cancer cell lines at a 10μM dose for their potential anticancer activity. Results: The two active compounds (8a, 10a) showed strong inhibitory effect against different cell lines, with highest inhibition against breast cancer panel. To elucidate the underlying molecular mechanisms, these compounds were examined for their clonogenic potential and anchorage-independent growth of estrogen receptor positive (MCF7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-468) breast cancer cells and investigated for induction apoptotic pathways. Conclusion: The outcomes from the current study will add much to the existing knowledge of the breast cancer research. This provides a rewarding conclusion and opens the way for future researchers to design and synthesize the novel active compounds against breast cancer.

AB - Background: Triazole based drugs are widely used in cancer patients for the treatment of life-threatening invasive fungal infections. A recent report on the usefulness of 1,2, 3- triazole scaffold for the inhibition of tyrosine kinases stimulated our curiosity to design new molecules based on this moiety. Methods: A series of new heterocyclic compounds containing 1,2,3 triazole moiety tethered to substituted vanillin or isovanillin were synthesized and analysed for their anticancer activity. The cyclopen-tyl/cyclohexyl ethers derived from vanillin and isovanillin were subsequently treated with MeMgI to give the carbinols. Reaction of these carbinols with TMSN3 and ZrCl4 as Lewis acid gave the desired azides. Click chemistry on azides with diverse acetylenes furnished the triazoles. The new triazole hybribs were screened o against 60 human cancer cell lines at a 10μM dose for their potential anticancer activity. Results: The two active compounds (8a, 10a) showed strong inhibitory effect against different cell lines, with highest inhibition against breast cancer panel. To elucidate the underlying molecular mechanisms, these compounds were examined for their clonogenic potential and anchorage-independent growth of estrogen receptor positive (MCF7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-468) breast cancer cells and investigated for induction apoptotic pathways. Conclusion: The outcomes from the current study will add much to the existing knowledge of the breast cancer research. This provides a rewarding conclusion and opens the way for future researchers to design and synthesize the novel active compounds against breast cancer.

KW - Anticancer

KW - Apoptosis

KW - Breast cancer

KW - Cancer therapy

KW - Molecular hybrids

KW - Triazole-vanillin

UR - http://www.scopus.com/inward/record.url?scp=85027887091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027887091&partnerID=8YFLogxK

U2 - 10.2174/1573407213666161128121435

DO - 10.2174/1573407213666161128121435

M3 - Article

AN - SCOPUS:85027887091

VL - 13

SP - 223

EP - 235

JO - Current Bioactive Compounds

JF - Current Bioactive Compounds

SN - 1573-4072

IS - 3

ER -