Structure-activity study to develop cationic lipid-conjugated haloperidol derivatives as a new class of anticancer therapeutics

Krishnendu Pal, Subratakumar Pore, Sutapa Sinha, Rajiv Janardhanan, Debabrata Mukhopadhyay, Rajkumar Banerjee

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20 Scopus citations


Haloperidol (HP), a neuroleptic drug, shows high affinity toward-receptors (SR). HP and reduced-HP at higher concentration were known to induce apoptosis in SR-overexpressing carcinomas and melanomas. Herein, we report the development of cationic lipid-conjugated haloperidol as a new class of anticancer therapeutics. In comparison to HP, the C-8 carbon chain analogue (HP-C8) showed significantly high, SR-assisted antiproliferative activity against cancer cells via caspase-3-mediated apoptosis and down-regulation of pAkt. Moreover, melanoma tumor aggressiveness in HP-C8-treated mice was significantly lower than that in HP-treated mice. HP-C8 simultaneously reduced Akt-protein level and increased Bax/Bcl-2 ratio in vascular endothelial cells, thereby indicating a possible protein kinase down-regulatory and apoptosis inducing role in tumor-associated vascular cells. In conclusion, we developed-receptor-targeting cationic lipid-modified HP derivatives as a promising class of anticancer therapeutic that concurrently affects cancer and tumor environment associated angiogenic vascular cells through induction of apoptosis and Akt protein down-regulation.

Original languageEnglish (US)
Pages (from-to)2378-2390
Number of pages13
JournalJournal of Medicinal Chemistry
Issue number7
StatePublished - Apr 14 2011


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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