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.
N1 - Funding Information:
This work was partially funded by Council of Scientific and Industrial eR search, New Delhi, India under 12 th plan for SMILE and ORIGIN (CSC-0108) projects at CSI-RIICT, Hyderabad; NCI 01 CR A131294, 21 CR A155686 and Breast Cancer Research Foundation and the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and the Stanford University startup grant to SVM. KS is thankful to IICT-RMIT eR search program (CLP-0092) for the financial support in the form research fellowship. HH is thankful to RMIT, Melbourne, Australia, for research grant.
Publisher Copyright:
© 2017 Bentham Science Publishers.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
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
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U2 - 10.2174/1573407213666161128122552
DO - 10.2174/1573407213666161128122552
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 -