Coumarin compounds have been known to possess anti-inflammatory, antioxidant, antiallergic, hepatoprotective, antithrombotic, antimicrobial, anti-arrythmic, anti-osteoporosis, antiviral, and anticarcinogenic activities. Due to these wide variety of pharmacological values, Coumarins and its derivatives have got more importance in synthesis and production. The present study was aimed on two main parts. Firstly, investigating cytotoxic and apoptotic activities of different position of geranyl group alongside the Coumarin backbone on HeLa (cervical cancer) and HDF (human dermal fibroblast) by MTT assay in vitro. Furthermore, studying and an emphasis on the importance of the relationship between structure and activity in geranyloxycoumarin compounds was another aim of this research. The cytotoxic effect of 3-geranyloxycoumarin (3-GC), 4-geranyloxycoumarin (4-GC), 5-geranyloxycoumarin (5-GC), 6-geranyloxycoumarin (6-GC) and 8-geranyloxycoumarin (8-GC), which have been synthesized by mimicking the structure of 7-geranyloxycoumarin (auraptene), was assessed by MTT assay and the apoptosis inducing potential of these mentioned coumarin compounds was determined by flow cytometry. The results of MTT assay revealed that 3-GC, 4-GC, 5-GC, 6-GC and 8-GC had significant cytotoxic effect on HeLa cells. Additionally, the study of the toxicity of these compounds on HDF cells showed that they do not have cytotoxic effect on this cell line. Moreover, the flow cytometric analysis, using PI / FITC-Annexin V, showed that 3-GC, 4-GC, 5-GC, 6-GC, 8-GC induced apoptosis in HeLa cancer cells Altogether, our results indicate that changes in the level of cellular toxicity on HeLa cells is associated with the position of the gerenyl group; which puts an emphasis on the importance of the relationship between structure and activity in coumarin compounds. Our results showed that position 6 was the best site for the gerenyl group. Further studies on various cancer cell lines are required to confirm these findings and future studies need to be focused on the molecular mechanisms of toxicity inducing potential of these compounds both in vitro and in vivo.

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