A variety of benzo [6,7] cyclohepta [1,2-b] pyridine derivatives have been evaluated for their in vitro anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Among tested compounds, a exhibited potent antiproliferative activity against IMR32 with GI50 value less than 0.01 μM and compounds d, l and n exhibited promising anti-proliferative activity against IMR32 with GI50 values 0.1, 0.21 and 0.21 μM, respectively. This is the first report on in vitro anti-proliferative evaluation of benzo [6,7] cyclohepta [1,2-b] pyridine derivatives in addition to anti-inflammatory activity.                                                                                                  

Benzosuberone motif has remarkable biological activities such as anti-inflammatory, anti-pyretic, anti-ulcer, CNS-depressant, CNS stimulant and anticonvulsant activities. And some of the derivativesare also known for anti-tumor activity in murine p338 cell line tests [1]. In addition these derivatives widely used in pharmaceutical applications, such as tricyclic antidepressants containingdibenzosuberone moieties mostly effect the autonomic and central nervous systems, and traditional anti-depressants, like amitriptyline [2], imipramine [3] and noxiptiline [4] which continue to be used as first-line drugs in treating depressive disorders.

Pyridyl compounds are of interest to organic chemists in recent years owing to their wide spectrum of physiological activity [5-10]. The condensed derivatives of pyridines play significant role in bioactive molecules, especially in the form of benzo [5,6] cyclohepta [1,2-b] pyridines which are structural analogues to benzosuberone. The benzo [5,6] cyclohepta [1,2-b] pyridine is an important core biologically active compound with diverse biological activities, such as antihistamine as well as antitumor and antiinflammatory activities [11-17]. It is a highly potent pharmacophore and widely used in drug molecular design. Because of the important aforementioned properties of benzocyclohepta [1,2-b] pyridines derivatives, preparation of this heterocyclic nucleus has gained great importance in organic synthesis.

Recently, we have published [18] synthesis and anti-inflammatory activity of benzo [6,7] cyclohepta [1,2-b] pyridines, in the present manuscript, presenting in vitro anti-proliferative activity of benzo [6,7] cyclohepta [1,2-b] pyridines against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma) and a SRB cell proliferation assay to estimate viability or growth in addition to anti-inflammatory activity in continuation to our ongoing research activities [9-27], to discover and develop tumor growth inhibitors and apoptotic inducers as potential new anti-cancer agents.

Effects of the Compounds on the Viability of Human Cancer Cells

All the synthesized compounds of benzo [6,7] cyclohepta [1,2-b] pyridine derivatives (a-n) were screened for their in vitro antiproliferative activity against four cancer cell lines such as HeLa(cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma) .

The compounds were picked for an advanced assay against these four human cancer cell lines at five concentrations (0.01, 0.1, 1, 10, 100 μM). GI50 (growth inhibitory activity) was calculated and these values corresponded to the concentration of the compound causing 50

Taken together, we have synthesized a series of benzo [6,7]cyclohepta [1,2-b] pyridine derivatives (a-n) in good yields and performed there in vitro anti-proliferative activity against four different human cancer cell lines, HeLa, MIAPACA, MDA-MB-231 and IMR32. Compound a exhibited potent anti-proliferative activity against IMR32 with GI50 value less than 0.01 μM, which was more active than standards Doxorubicin and Paclitaxel in addition to anti-inflammatory activity.