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The present work describes the synthesis,conformation and cytotoxic activities of short β/γ hybrid peptides, Boc-β2,2-Ac 6 c-Gpn-NHMe, BG1 ; Boc-(β2,2-Ac 6 c-Gpn) 2 -OMe, BG2 ; Boc-(β2,2-Ac 6 c-Gpn) 3 -OMe, BG3 ; H-β2,2-Ac 6 c-Gpn-NHMe, BG4 ; H-(β2,2-Ac 6 c-Gpn) 2 -OMe, BG5; H-(β2,2-Ac 6 c-Gpn) 3 -OMe, BG6, Boc-β2,2-Ac 6 c-Gpn-OMe, BG7 and H-β2,2-Ac 6 c-Gpn-OMe, BG8. Mixed C 6 /C 7 conformations were observed for β/γ hybrid peptides. Further, BG1 - BG8 were screened against MCF-7 (Breast cancer), A549 (Lung Cancer), PC-3 (Prostate cancer), HCT-116 (Colon cancer), and MDA-MB-231 (Breast cancer) cell lines. Among all, BG6 exhibited potent cytotoxicity against all cancer cell lines with IC 50 ranging from 1.6 μM to 6.3 μM with relatively low cytotoxicity against normal epithelial breast cell line fR-2 and human embryonic kidney cell line HEK-293. Minimal hemolytic activity was observed for BG6 against human erythrocytes. Peptide BG6 displayed anti-migratory and anti-invasive potentials showing strong interactions with intrinsic apoptotic markers Bcl-2, Bax, and cleaved-PARP, as well as the induction of the mitochondria maladjustment mediated apoptosis. [Display omitted] • Short β/γ hybrid peptides containing conformationally constrained amino acids exhibited C 6 /C 7 conformation. • Hybrid peptides BG1-BG8 were screened against MCF-7 (Breast cancer), A549 (Lung Cancer), PC-3 (Prostate cancer), HCT-116 (Colon cancer), and MDA-MB-231 (Breast cancer). • BG6 exhibited potent anticancer activity with IC 50 1.619 μM and 2.251 μM against MCF-7 and HCT-116, respectively. • BG6 showed anti-proliferative, antimigratory and anti-invasive potentials. • BG6 showed strong interactions with Bcl-2, Bax, and cleaved-PARP together with the induction of the mitochondria maladjustment mediated apoptosis. [ABSTRACT FROM AUTHOR]

A series of new β -arylated arteannuin B analogues were synthesized through its coupling with arylboroic acids and were evaluated for their in vitro cytotoxic activity in a panel of six cancer cell lines. All of the new compounds 3b , 3d , 3i , 3j and 3n displayed potent cytotoxic potential with an IC 50 from 1.8 to 18 µm in various cell lines. Furthermore, compound 3i was proven to be the most potent cytotoxic and anti-proliferative compound in all the six distinct cell lines. Compound 3i exhibited promising apoptosis inducing potential in breast cancer cells and stalled their wound healing properties and thus proven effective to block migration of cancer cells. [Display omitted] • Palladium catalyzed β -arylated arteannuin B fourteen analogues were synthesized through coupling with arylboroic acids at the exocyclic double bond in the lactone ring. • All the compounds were evaluated invitro cytotoxic activity in six cancer cell lines in which compounds 3b , 3d , 3i , 3j and 3n displayed potent cytotoxic potential with an IC 50 from 1.8 to 18 µm. • Compound 3i proven the most potent cytotoxic, anti-proliferative in all the six cell lines, and exhibited promising apoptosis in breast cancer cells and wound healing properties. • The docking pose of the ligand 3i exhibits several interactions with GRP78 residues with binding energy of -8.07 kcal/mol. We have recently highlighting the role of spiroisoxazoline arteannuin B derivatives in mediating proinflammatory cytokines like IL-6, TNfα and NO in vitro. In the present study, a series of new β -arylated arteannuin B analogues were synthesized through coupling with arylboroic acids and evaluated for their in vitro cytotoxic activity in a panel of six cancer cell lines. The binding efficiency was verified by docking of the original ligand within the active site of ATPase domain of GRP78 (PDB ID: 3LDL) at a resolution of 2.30 Å with the score energy of −8.07 kcal/mol. Among the new compounds 3a, 3b , 3d , 3i , 3j and 3n displayed potent cytotoxic potential with an IC 50 from 2 to 18 µM and compound 3i was proven to be the most potent cytotoxic and anti-proliferative compound of all the six distinct cell lines. Compound 3i exhibited promising apoptosis inducing potential in breast cancer cells and stalled their wound healing properties and was effective in blocking the migration of cancer cells. [ABSTRACT FROM AUTHOR]