الفهرس 
Natural and synthetic coumarinsOnly 14 pages are availabe for public view
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Abstract
Thousands of coumarin compounds have been isolated an d
ident if ied in di fferent plant species. These compounds play an
important role in ant icancer drug development due to thei r wide
range of biological act ivi t ies and their ef fect against di fferent
types of cancer cel ls. Therefore, this study was car ried out to
gain informat ion about the mechanism of these compounds and
searching for novel cytotoxic agents. Seven plants containing
coumarin derivat ives and ten new furocoumarin analogues were
used in this work. HepG-2 cel ls (l iver cancer cel l l ine) were
treated wi th concent rat ions ranged f rom 0.1 - 1 0 0 0 μ g /ml f o r 7 2
hours. Compound number 9 showed highest reduct ion in cel l
viabi l i ty percentage, and exhibi ted the highest inhibi tory
act ivi ty wi th IC50 ( inhibi tory concent rat ion for 50% of cel ls)
equal 11.97 μ g/ml , a n d f al l wi t h i n t h e Ame r i ca n Na t i o n al
Cancer Inst i tute cr i teria; whi le the other compounds recorded
medium or weak ef fect as compared wi th the standard drug
Doxorubicin (IC50=0.87 μ g /ml ) . The plant extracts also reduced
the viabi l i ty of cancer cel ls in a dose dependent manner . Their
cytotoxic ef fect was more observed at the higher concentrat ions.
IC50 of the seven plant extracts was ranged f rom 121.4 μg/ml
for Verbascum thapsus to 511.8 μg/ml for Ammi majus.
Root t ip cel ls of Pisum sat ivum plant were t reated wi th
concent rat ions ranged f rom 0.05–1.0 mg/ml of compounds
number 9 and 8 and wi th 2.19 – 35 mg/ml for the natural plant
extracts of Achi l lea mi l lefol ium and Verbascum thapsus . Resul ts
showed signi ficant decrease in mi tot ic index that increased
gradual ly by increasing the concent rat ion and the t ime of
treatments; in addi t ion to di fferent types of mi tot ic
abnormal i t ies were recorded such as st ickiness and chromosome
breakage. The expression level of two cel l cycle regulatory
genes; cycl in B1 and cycl in D1 were examined using RT-PCR
techniques. The resul ts indicated that cycl in B1 was down
regulated in response to t reatment of Pisum sat ivum roots wi th
the concent rat ions 0.5 mg/ml of compound 9 and 1.0 mg/ml of
compound 8, and wi th 17.5, 35 mg/ml of the ext racts of
Verbascum thapsus and Achi l lea mi l lefol ium as compared wi th
the reference gene β- tubul in-3. Moreover, only compound
number 9 caused decrease in cycl in D1 in response to treatment wi th 0.5 mg/ml , as compared wi th compound number 8; ext racts
of Verbascum thapsus and Achi l lea mi l lefol ium which showed
no effect , indicat ing the effect of compound number 9 on the
cel l cycle ar rest at the t ransi t ion point G1 /S. The genomic
stabi l i ty percentage in Pisum sat ivum plant cel ls t reated wi th
the previous materials using ISSR-DNA fingerprints showed
change in band number and decrease in genomic template
stabi l i ty (GTS) values in al l treatments. Compound number 9
recorded the lowest GTS (46%) whi le compound number 8
recorded 64% in comparison to the untreated cont rol , indicat ing
that compound 9 is more ef fect ive on genome stabi l i ty. The
GTS value of plant ext racts decreased wi th increasing the
concent rat ions. The lowest GTS (76.12%) recorded wi th the
highest concent rat ion (35 mg/ml) of Verbascum thapsus; whi le
recorded 88.06% in samples treated wi th the same concent rat ion
of Achi l lea mi l lefol ium. Thus, 0.5 mg/ml of compound 9 have
g r ea t e r d ama g e o n c el l ’ s g en et i c mat er i al i n d i c at i v e o f t h e
genotoxici ty at this concentrat ion. On the other hand, the
molecular docking technique showed that this compound has a
good abi l i ty to inhibi t topoisomerase I which in turn wi l l lead to
cancer cel l inhibi t ion through the inhibi t ion of DNA repl icat ion.