726
M. Bia6a et al. / Il Farmaco 54 (1999) 721–727
M. marinum 6423, and M. a6ium 103317 are listed in
Table 3. None of the investigated compounds was
found to be active against Candida albicans, Candida
sp, Cryptococcus neoformans, Gram-positive or Gram-
negative bacteria, and isolates of pathogenic plant
fungi, and data are not displayed, with the exception of
12a against Phomopsis sp. (MIC=0.25 mg/ml).
22c, where cinnamyl moiety is present, proved to be
active.
Regarding the replacement of the imidazole with
N-methylpiperazine, morpholine and thiomorpho-
line moieties, no particular difference was observed
when the cinnamyl substituent was maintained,
whereas the activity against atypical mycobacteria
increases when imidazole or N-methylpiperazine or
morpholine moieties and p-Cl-phenyl or biphenyl
ones are simultaneously introduced in the molecule,
with the exception of M. smegmatis.
4.1. Antimycobacterial acti6ity
Interesting results were obtained from these assays,
and data are reported in Table 3. Among the tested
compounds, 11b, 11c, 12b, 14a, 14c, 16c, and 18c
exhibited an interesting activity against M. tuberculosis,
even though all of them proved to be less active than
the controls. Against M. marinum not only were com-
pounds 11c, 14a, 14b, 14c, 16a and 16c active, but they
were also found to be more active than the reference
compounds and in particular 14a and 14c were the
most active. However, compounds 11b, 15a, 15b, 15c,
16b, 16c, 20b, 22b and 22c, showed good activity,
considering the fact that all of them are more active
than Isoniazid and Streptomycin. Compounds 11b, 11c,
12b, 14a, 14b, 15b, 16c, 17a and 19c proved to be active
against M. gordonae, and all of them were much more
active than the controls. Against M. a6ium the most
active compounds were 11c, 12b and 14a, but interest-
ing activity was also shown by compounds 11b, 12c,
15a, 16a, 19b and 22c which were more active than
Isoniazid and Streptomycin.
In conclusion, comparing the new derivatives with
the other compounds mentioned above and described
in depth in earlier works [4,5], we can affirm that in
general the new derivatives are less toxic, more active
against M. gordonae and M. marinum, and less active
against M. a6ium, while their activity against M. tuber-
culosis is almost the same.
The obtained results suggest further modifications to
the lead compound 1, and studies are in progress on
this topic.
Acknowledgements
Supported (in part) by the National Tubercolosis
Project (ISS-Ministero della Sanita` grant No. 96/D/T48
and by a contribution of the Istituto Pasteur Fon-
dazione Cenci-Bolognetti Universita` di Roma ‘La
Sapienza’.
It is important to point out the generally low toxicity
shown by all the new compounds, but in particular by
compound 12b, which proved to be very active against
M. marinum, M. gordonae, and M. a6ium. This result is
very important considering what has been reported
about disseminated M. a6ium complex infections mak-
ing a substantial contribution to both increased illness
and death in patients with AIDS [14].
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We confirmed that ortho and para derivatives are the
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In general, contrary to what was reported by Bar-
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