Effects of skeletal modifications of ciprofloxacin on ... - ResearchGate

194 JOURNAL <strong>of</strong> CHINESE CLINICAL MEDICINE VOLUME 2|NUMBER 4|April 2007
Table 3 Results <strong>of</strong> Screening Cipr<strong>of</strong>loxacin (1) and its Derivatives (2 -13) for their Antifungal Activity in vitro ( zone <strong>of</strong> in唱
hibition in mm)
Test fungi
Compound No. A B 1 2 3 4 5 6 7 8 9 10 11 12 13
Trichophytonlongifusus 100 0 0 0 0 0 0 0 60 60 0 25 0 0 0
Candida albicans 100 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Aspergillus flavus 0 100 0 0 0 0 0 0 60 0 0 45 0 0 0
Microsporum canis 100 0 0 0 0 0 0 0 55 55 0 50 0 50 0
Fusarium solani 100 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Candida glaberata 100 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Note:A =Miconazole;B =Amphotericine B
on cipr<strong>of</strong>loxacin (1).These preliminary studies provide
us lead compounds like 2,4,9,and 12 for further modi唱
fications at nitrogen <strong>of</strong> piperazine or other active posi唱
tions like carboxylic acid residue or the ketonic carbon唱
yl function.It may be envisioned that the <strong>modifications</strong>
at nitrogen <strong>of</strong> piperazine residue and other two seem唱
ingly active positions may result into a better antibiotic
with the minimization <strong>of</strong> its side effects.
Antifungal Activity
An interesting feature <strong>of</strong> the present study is that when
all synthesized compounds (1 ~12) along with cipro唱
floxacin (1) were randomly screened for 6 fungal
strains i.e.Trichophyton longifusus,Candida albicans,
Aspergillus flavus,Microsporumcanis,Fusarium solani
and Candida glaberata,it is revealed that cipr<strong>of</strong>loxacin
(1 ) was inactive against any <strong>of</strong> the fungal strains
used.Nevertheless,compound 7 showed good activities
against Trichophyton longifusus,Aspergillus flavus and
Microsporumcanis.Compound 8 was found to be active
against Trichophyton longifusus and Microsporum canis
strains.Compound 10 showed moderate activities a唱
gainst Aspergillus flavus and Microsporum canis,while
compound 12 was found to be moderately active against
Microsporumcanis. Antifungal activity in cipr<strong>of</strong>loxacin analogues may
open new avenues for designing antifungal agents based
on cipr<strong>of</strong>loxacin (1) skeleton.For enhancing the anti唱
fungal strength <strong>of</strong> the lead molecules 7,8,10,and 12,
either modification in the alkyl side chain <strong>of</strong> compound
6 and 7 or by varying the substitution <strong>of</strong> phenyl ring in
compound 10 and 12.In addition,the synthetic modifi唱
cations on carboxyl group or ketonic carbonyl function
may enhance the antifungal activity.
Cytotoxic Activity
Bioactive compounds are <strong>of</strong>ten toxic to Artemia salina
( leach, brine shrimp ) larvae.The bioassay method
adopted is rapid and inexpensive which has been devel唱
oped for screening and monitoring <strong>of</strong> physiologically
active compound.
During this experiment etoposide is used as stan唱
dared drug and LD50 is found to be 0畅178 μg /ml while
it has been found that neither cipr<strong>of</strong>loxacin nor its de唱
rivatives is cytotoxic.
CONCLUSION
The <strong>skeletal</strong> <strong>modifications</strong> <strong>of</strong> cipr<strong>of</strong>loxacin (1) showed
a varying degree <strong>of</strong> antimicrobial activities particularly
compound 2,4,9,and 12 exhibited promising antimi唱
crobial activities devoid <strong>of</strong> any toxicity and may be
used as lead compounds for further investigations.Ad唱
ditionally compound 7,8,10,and 12 exhibited encoura唱
ging antifungal activities and provided a base to explore
the antifungal activities <strong>of</strong> cipr<strong>of</strong>loxacin (1) skeleton
containing molecules.Further research based on over
preliminary results may lead to a new class <strong>of</strong> com唱
pounds having antifungalproperties. REFERENCES
1.Crumplin GC,Smith JT.Nalidixic acid bacterial chromosome replica唱
tion.Nature,1976,260 :643 -645.