2. Academic Validation
  3. Novel alkylphospholipid-DTC hybrids as promising agents against endocrine related cancers acting via modulation of Akt-pathway

Novel alkylphospholipid-DTC hybrids as promising agents against endocrine related cancers acting via modulation of Akt-pathway

  • Eur J Med Chem. 2014 Oct 6:85:638-47. doi: 10.1016/j.ejmech.2014.08.028.
Santosh Jangir 1,  Veenu Bala 2,  Nand Lal 1,  Lalit Kumar 1,  Amit Sarswat 1,  Amit Kumar 3,  Hamidullah 3,  Karan S Saini 3,  Vikas Sharma 3,  Vikas Verma 3,  Jagdamba P Maikhuri 3,  Rituraj Konwar 3,  Gopal Gupta 3,  Vishnu L Sharma 4
Affiliations

Affiliations

  • 1 Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
  • 2 Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific & Innovative Research, New Delhi 110001, India.
  • 3 Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
  • 4 Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific & Innovative Research, New Delhi 110001, India. Electronic address: vlscdri1@rediffmail.com.
PMID: 25128666 DOI: 10.1016/j.ejmech.2014.08.028
Abstract

A new series of 2-(alkoxy(hydroxy)phosphoryloxy)ethyl dialkylcarbodithioate derivatives was synthesized and evaluated against endocrine related cancers, acting via modulation of Akt-pathway. Eighteen compounds were active at 7.24-100 μM against MDA-MB-231 or MCF-7 cell lines of breast Cancer. Three compounds (14, 18 and 22) were active against MCF-7 cells at IC50 significantly better than miltefosine and most of the compounds were less toxic towards non-cancer cell lines, HEK-293. On the Other hand, twelve compounds exhibited cell growth inhibiting activity against prostate Cancer cell lines, either PC-3 or DU-145 at 14.69-95.20 μM. While nine of these were active against both cell lines. The most promising compounds 14 and 18 were about two and five fold more active than miltefosine against DU-145 and MCF-7 cell lines respectively and significantly down regulated phospho-Akt. Possibly anti-cancer and pro-apoptotic activity was mostly due to blockade of Akt-pathway.

Keywords

Akt-pathway; Alkylphospholipid; Anti-proliferative agent; Dithiocarbamate; Endocrine cancer; Miltefosine.

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