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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In an attempt to develop potent anti-tubulin agents against most dreadful disease cancer, a library of 28 novel triazole tethered isatin-coumarin hybrids were synthesized by click chemistry approach. Synthesized hybrids were characterized and evaluated against a panel of human cancer cell lines viz. THP-1, COLO-205, HCT-116 and PC-3. Biological assay unveiled that, compounds A-1 to A-6, B-1 to B-4 and C-1 to C-3 displayed significant inhibitory potential against THP-1, COLO-205 and HCT-116 cell lines which were more sensitive towards the designed hybrids. PC-3 among these cell lines was found to be almost resistant. Established SAR revealed marked dependence of the cytotoxic activity on the type of substituent on isatin and the length of carbon-bridge connecting isatin moiety with triazole ring. Unsubstituted isatin and two carbon-bridge were found to be crucial for cytotoxicity. Three most potent hybrids (A-1, A-2 and B-1) were further tested for tubulin polymerization inhibition. Among these three compounds, A-1 found to be endowed with most prominent tubulin polymerization inhibition potential with IC50 value of 1.06 µM which was further confirmed by using confocal microscopy. Possible binding interactions between the most potent hybrid molecule A-1 and tubulin were also divulged by molecular modeling studies.

Original languageEnglish
Pages (from-to)3974-3979
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number17
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

Fingerprint

Isatin
Triazoles
Tubulin
Cells
Cell Line
Polymerization
Carbon
Click Chemistry
HCT116 Cells
Molecular modeling
Confocal microscopy
Cytotoxicity
varespladib methyl
Confocal Microscopy
Biological Assay
Inhibitory Concentration 50
Libraries
Assays
Neoplasms
Molecules

Keywords

  • Anti tubulin
  • Antitumor
  • Coumarin
  • Docking
  • Hybrid
  • Isatin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 17, 01.01.2017, p. 3974-3979.

Research output: Contribution to journalArticle

Singh, Harbinder ; Singh, Jatinder V. ; Gupta, Manish K. ; Saxena, Ajit K. ; Sharma, Sahil ; Nepali, Kunal ; Bedi, Preet Mohinder S. / Triazole tethered isatin-coumarin based molecular hybrids as novel antitubulin agents : Design, synthesis, biological investigation and docking studies. In: Bioorganic and Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 17. pp. 3974-3979.
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