Journal of Chemical Sciences

, Volume 128, Issue 8, pp 1245–1263 | Cite as

Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: Active inducers of testicular germ cell apoptosis

  • ANIL K SINGH
  • JITENDER K BHARDWAJ
  • ANA OLIVAL
  • YOGESH KUMAR
  • AVIJIT PODDER
  • ANKUR MAHESHWARI
  • RENUKA AGRAWAL
  • N LATHA
  • BRAJENDRA K SINGH
  • HELENA TOMÁS
  • JOÃO RODRIGUES
  • RAM KISHAN
  • B RUPINI
  • BRIJESH RATHI
Article

Abstract

Understanding of apoptosis or programmed cell death has provided the basis for novel therapeutics that has resulted in rationally designed anticancer strategies. Recently, inducers of apoptosis have been used in cancer therapy. In this work, we describe the role of chiral phthalimides functionalized with piperazines as potential apoptotic inducers. The listed twenty phthalimides were assessed for their in vitro apoptotic activity against testicular germ cells. All phthalimides showed a significant apoptotic response (∼39 to ∼68%). TUNEL assay and acridine orange fluorescence staining were carried out to investigate the molecular mechanisms responsible for the cell death. Phthalimides exhibited substantial apoptotic induction following the intrinsic pathway mechanism. Studies advocated that the apoptotic induction was mediated through caspase-9, caspase-3, JNK MAP kinase and tumor suppressor p53, which was accompanied by DNA fragmentation and nuclear condensation. Besides, the best five phthalimides regarding apoptotic action were evaluated for in vitro cytotoxic effects against CAL-72 and MCF-7 cancer cell lines. Compounds showed efficient killing of cancer cells. This discovery of functionalized phthalimides as apoptotic inducers would be highly valuable in understanding the mechanism of apoptosis at the molecular level and opens up new possibilities for therapeutic strategies.

Graphical Abstract

A new class of phthalimides functionalized with piperazines were prepared, characterized and validated as active inducers of apoptosis against testicular germ cells as advocated by histological and molecular techniques.

Keywords

Phthalimides apoptosis molecular docking aryl piperazine cancer cells 

Supplementary material

12039_2016_1122_MOESM1_ESM.doc (5.2 mb)
(DOC 5.18 MB)

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Copyright information

© Indian Academy of Sciences 2016

Authors and Affiliations

  • ANIL K SINGH
    • 1
  • JITENDER K BHARDWAJ
    • 2
  • ANA OLIVAL
    • 3
  • YOGESH KUMAR
    • 1
  • AVIJIT PODDER
    • 4
  • ANKUR MAHESHWARI
    • 5
  • RENUKA AGRAWAL
    • 6
  • N LATHA
    • 4
  • BRAJENDRA K SINGH
    • 1
  • HELENA TOMÁS
    • 3
  • JOÃO RODRIGUES
    • 3
  • RAM KISHAN
    • 7
  • B RUPINI
    • 8
  • BRIJESH RATHI
    • 9
  1. 1.Bioorganic Research Laboratory, Department of ChemistryUniversity of DelhiDelhiIndia
  2. 2.Reproductive Physiology Laboratory, Department of ZoologyKurukshetra UniversityKurukshetraIndia
  3. 3.CQM-Centro de Química da Madeira, MMRGUniversidade da MadeiraFunchalPortugal
  4. 4.Bioinformatics Infrastructure Facility, Sri Venkateswara CollegeUniversity of DelhiNew DelhiIndia
  5. 5.Department of Zoology, Zakir Husain Delhi CollegeUniversity of DelhiNew DelhiIndia
  6. 6.Department of Botany, Miranda HouseUniversity of DelhiDelhiIndia
  7. 7.Department of ChemistryUniversity of DelhiDelhiIndia
  8. 8.School of Agriculture, Environmental StudiesIndira Gandhi National Open UniversityNew DelhiIndia
  9. 9.Department of Chemistry, Hansraj CollegeUniversity of DelhiDelhiIndia

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