Background: Developing new chemotherapeutic agents with molecular targets, larger margin of
safety against normal cells and low cost is the target many scientists try to achieve.
Objective: The present study was undertaken to investigate the anticancer activity of a novel series of thiophene
compounds and the molecular mechanisms associated.
Method: A series of novel heterocyclic compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14,
and 15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9) was synthesized from 4,5,6,7-
tetrahydrobenzo[b] thiophene (1). The newly synthesized derivatives along with the parent compound were
evaluated for their anticancer activity against human HepG2, MCF7 and HCT116 cell lines and compared to
doxorubicin as a reference drug.
Results: Compound 7 was very selective in targeting only the colon cells. Compounds 1, 5, and 12 showed
strong cytotoxic activities against the 3 cell lines at 6-16 µM without any apparent toxicity to the normal fibroblasts
WI-38. They had DNA affinity at 29-36 µM. The three compounds enhanced apoptosis to varying degrees
elevating the expression of Bax, caspase 9 and caspase 3 in HepG2. Compound 5 was the most potent analogue
and was superior to the standard drug used in upregulating the apoptotic genes and inhibiting tyrosine kinase at
1 µM. The IC50 value for compound 5 against TK was 296 nM.
Conclusion: Taken together, this study presents some thiophene scaffolds as auspicious hits for further optimization
as specific antiproliferative agents against cancer cells and promising tyrosine kinase inhibitors at nanomolar