Anticancer phytochemical analogs 37: synthesis, characterization, molecular docking and cytotoxicity of novel plumbagin hydrazones against breast cancer cells.
We have synthesized, structurally characterized and examined cytotoxicity of novel plumbagin hydrazones against estrogen and progesterone receptor positive (ER+/PR+) MCF-7 and triple negative MDA-MB-231 breast cancer cell lines in order to evaluate the potential of these novel phytochemical analogs. Compounds were docked into the protein cavity of p50-subunit of NF-κB protein revealing better fit and better binding energies than the parent plumbagin compound. This was also reflected in their superior cytotoxicities which were found to be mediated by inhibition of NF-κB expression. These compounds can provide a starting point for the development of novel drug molecules against triple negative breast cancers.
ISTRA, Department of Chemistry, MCE Society's Abeda Inamdar Senior College of Arts, Science and Commerce, University of Pune, Pune 411001, India.
Prasad
P
Dandawate
Department of Pathology, Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine, Karmanos Cancer Institute, 707 HWCRC, 4100 John R St, Detroit, MI 48201, USA. Electronic address: ahmada@karmanos.org.
Aamir
A
Ahmad
Department of Bioinformatics and Computer Science, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411044, India.
Jyoti
J
Deshpande
Department of Bioinformatics and Computer Science, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411044, India.
K Venkateswara
KV
Swamy
ISTRA, Department of Chemistry, MCE Society's Abeda Inamdar Senior College of Arts, Science and Commerce, University of Pune, Pune 411001, India.
Ejazuddin M
EM
Khan
Department of Bioinformatics and Computer Science, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune 411044, India.
Madhukar
M
Khetmalas
ISTRA, Department of Chemistry, MCE Society's Abeda Inamdar Senior College of Arts, Science and Commerce, University of Pune, Pune 411001, India; Department of Pathology, Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine, Karmanos Cancer Institute, 707 HWCRC, 4100 John R St, Detroit, MI 48201, USA. Electronic address: sbpadhye@hotmail.com.
Subhash
S
Padhye
Department of Pathology, Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine, Karmanos Cancer Institute, 707 HWCRC, 4100 John R St, Detroit, MI 48201, USA.
Fazlul
F
Sarkar
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006835:Hydrazones; D009285:Naphthoquinones; C014758:plumbagin
Breast cancer; Molecular docking; NF-κB; Plumbagin