(
)
16
S.N. Pandeya et al.rPharmaceutica Acta HelÕetiae 74 1999 11–17
Table 5
Anti-HIV activity
2.2.3. Anti-HIV actiÕity
The procedure to measure anti-HIV activity in MT-4
a
b
Compound
EC50 mM
CC50 mM
SIc
Ž
.
Ž
.
Ž
.
cells has been described previously Pandeya et al., 1998a .
Either mock-infected or HIV-1 infected MT-4 cells were
incubated in the presence of various concentrations of test
compounds and the number of viable cells was determined
S-1
S-2
S-3
S-4
S-5
S-6
S-7
S-8
S-9
S-10
S-11
S-12
)57
)11
)9
)17
)40
)15
)10
)14
)8
56.7
11.1
9.1
16.8
40.3
15.3
10.4
13.9
7.8
-1
-1
-1
-1
-1
-1
-1
-1
-1
-1
-1
-1
w Ž
.
by the MTT 3- 4,5 dimethyl thiazol-2-yl -2, 5-diphenyl
x
tetrazolium bromide method on day five after virus infec-
tion.
)16
)10
)10
16.3
10.2
9.5
3. Results and discussion
All the synthesized compounds were tested for in vitro
antibacterial activity by the agar dilution method. The
MICs of the compounds against 26 pathogenic bacteria are
presented in Tables 2 and 3. Also included is the activity
of reference compounds sulfamethoxazole and trimetho-
prim. It has been observed that all the compounds tested
showed mild to moderate activity against tested bacteria.
a Effective concentration of compound to achieve 50% protection in MT-4
cells against the cytopathic effect of HIV-1.
bCytotoxic concentration of compound, required to reduce the viability of
mock infected MT-4 cells by 50%.
cSelectivity index: ratio of CC50 rEC50
.
Ž
.
All the compounds showed higher activity smaller MIC
the reactivity profile was very high with morpholino
derivative. For example against E. faecalis dimethylamino
Mannich base S-2 have MIC of 312.5 mgrml and mor-
pholino derivative have 9.76 mgrml. As regard to the
substitution in the 5th position of isatin molecule, the order
of reactivity is Cl)Br)H. In case of antifungal activity,
structure activity relationship was parallel to that of the
than sulfamethoxazole except against Pseudomonas aerug-
inosa. When compared to trimethoprim all the compounds
are more active against Salmonella typhimurium, Staphy-
lococcus aureus, Pseudomonas aeruginosa, Aeromonas
hydrophile, Vibrio cholerae-01, Bacillus subtilis and Pro-
teus rettgeri, five compounds are more active against
Edwardsiella tarda, seven compounds are more active
against Enterococcus faecalis, six compounds are equipo-
tent and two compounds are more active against Shigella
flexnari.
The antifungal activity of the compounds was studied
with the eight pathogenic fungi. The results are summa-
rized in Table 4. Clotrimazole has been used as reference
for inhibitory activity against fungi. All the compounds
showed significant antifungal activity. When compared to
X
X
Ž
antibacterial activity. Compound 5-chloro-3- 3 ,4 -dihydro-
X
X
X
.
2 -methylmercapto-4 -oxoquinazolin-3 -yl -1-morpholino
methyl imino isatin was the most active antimicrobial
compound.
The synthesized compounds were evaluated for their
inhibitory effect of the replication of HIV-1 in human
MT-4 cells. None of the compounds showed marked anti-
HIV activity at a concentration significantly below their
Ž
.
toxicity threshold Table 5 .
Ž
.
clotrimazole, five compounds are equipotent 4.88 mgrml
Ž
.
and five compounds are more active 2.44 mgrml against
Ž
.
M. audouinii, five compounds are equipotent 2.44 mgrml
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Pandeya
