title: Synthesis, characterization and anti-tumor activity of novel thymoquinone analogs against pancreatic cancer.
abstract: Thymoquinone (TQ), isolated from the seeds of Nigella sativa, show moderate efficacy against pancreatic cancer. In the present work we report synthesis and characterization of novel TQ analogs appended with gallate and fluorogallate pharmacophores and evaluation of their effects against pancreatic cancer cell lines for cell viability and induction of apoptosis. The efficacy of the analogs alone or in combination with Gemcitabine was assessed in vitro. LC-MS spectra of ATQTHB and ATQTFB showed major peaks corresponding to expected M+1 fragment at 316.34 and 322.34 respectively. Molecular docking studies revealed good fit for these analogs in the COX-2 protein cavity with better binding energies compared to parent TQ compound. Present TQ analogs exhibit superior anti-proliferative activity, excellent chemo-sensitizing activity against pancreatic cancer in vitro and in combination with Gemcitabine.
authors.affiliation: ISTRA, Department of Chemistry, Abeda Inamdar College, University of Pune, Azam Campus, Pune 411001, India.
authors.forename: Mujahid
authors.initials: M
authors.lastname: Yusufi
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Banerjee
authors.forename: Momin
authors.initials: M
authors.lastname: Mohammad
authors.forename: Sandhya
authors.initials: S
authors.lastname: Khatal
authors.forename: K
authors.initials: K
authors.lastname: Venkateswara Swamy
authors.forename: Ejazuddin M
authors.initials: EM
authors.lastname: Khan
authors.forename: Amro
authors.initials: A
authors.lastname: Aboukameel
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Subhash
authors.initials: S
authors.lastname: Padhye
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D031881:Nigella sativa / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; C003466:thymoquinone