Page 63 - Book of Abstracts 2020

th
8 Biannual Conference on Chemistry - CHEM 08

1,4,5,6,7,8-Hexahydroquinoline and 5,6,7,8-

Tetrahydronaphthalene as a New Scaffold of Tubulin
Polymerization Inhibitors Inducing G2/M Phase Arrest and
Pre-G1 apoptosis: Design, Synthesis, Biological Evaluation,
and Computational Studies

2
Mennatallah Ali Shaheen , Ali abdel Rahman Al emam , Nadia
1
1,3
Sabry Gohary
Email: mennashaheen8@gmail.com

ABSTRACT

New series of 2-amino-1,4,5,6,7,8-hexahydroquinoline-3-carbonitriles 3a,b
and 2-amino-5,6,7,8-tetrahydronaphthalene-1,3-dicarbonitriles 4a-h were
prepared and evaluated for antimicrobial, antiquorum-sensing and
antitumor activities. Antimicrobial screening toward selected Gram-positive
and Gram-negative bacteria and fungi indicated that the
hexahydroquinoline-3-carbonitrile derivatives 3a and 3b, and the
tetrahydronaphthalene-1,3-dicarbonitrile derivative 4b have good
antimicrobial activity against E. coli and C. albicans. In addition, the
tetrahydronaphthalene-1,3-dicarbonitriles 4c and 4d exhibited good
antifungal activity against C. albicans. In vitro antiproliferative screening of
the new derivatives against HepG2, HCT-116 and MCF-7 cancer cells
revealed that the tetrahydronaphthalene-1,3-dicarbonitrile 4c is the most
active analog against all tested cell lines. It was subjected to further study
regarding its effect on cell cycle analysis, apoptosis assay, tubulin
polymerization inhibition, and different caspase activity. Further studies
indicated that compound 4c could induce the three tested cancer cells arrest
in the G2/M and induces pre-G1 apoptosis which prevented its mitotic cycle.
Besides, compound 4c displayed a remarkable inhibition of tubulin
polymerization with IC50 value 5.64 µM. Compound 4c showed caspase-3
induction with IC50= 448.5 and 331.5 ng/mL in HepG2 and HCT-116
respectively, and caspase-9 induction with IC50= 18.8 ng/mL in MCF-7 cells.
These results revealed that compound 4c is a promising tubulin
polymerization inhibitor and apoptotic inducer for treatment of cancer and it
is worthy of further exploitation. In silico simulation studies referred that
most of the new analogs comply with the optimum needs for good oral
absorption. Also, computational carcinogenicity evaluation was predicted.

BOOK OF ABSTRACTS CHEM 08 (2020) Page 62