9
34 H. M. Faidallah et al.
Derivatization of the sulfonamido group into sulfonylu-
reido functionality as in 11b (X = O, R = Cl) resulted in a
limited enhancement in the anti-Gram positive activity
and an observable improvement in the activity against E.
coli. On the contrary, the sulfonylthioureido 11c (X = S,
R = H) exhibited better spectrum of activity against the
Gram positive and Gram negative strains except K. pneu-
moniae when compared with the parent sulfonamide
(R = 4-F-C H ) offered a limited enhancement in the
6 4
activity against the Gram positive strains when compared
with the parent 21d.
Preliminary in vitro anticancer screening
Out of the newly synthesized compounds, twenty deriv-
atives 5c,d,f, 6a,b, 7c, 8b, 9b, 11c, 15a, 18b, 19b, 20b,
2
1a,b,d, 22b,d and 23b,d, were selected by the National
1
0. On the other hand, in spite of the inactivity of the
Cancer Institute (NCI) in vitro disease-oriented human
cells screening panel assay to be evaluated for their in
vitro antitumor activity. Effective one-dose assay has
been added to the NCI 60 Cell screen in order to increase
compound throughput and reduce data turnaround
time to suppliers while maintaining efficient identifica-
tion of active compounds. All compounds submitted to
the NCI 60 Cell screen, are now tested initially at a single
high dose (10 μM) in the full NCI 60 cell panel including
leukaemia, non-small cell lung, colon, CNS, melanoma,
ovarian, renal, prostate and breast cancer cell lines.
However, the data obtained from the one-dose assay
revealed that none of the tested compounds showed
significant antitumor activity and consequently, none
of them was promoted to the 5-dose assay.
key intermediate pyridone 12, introducing a benzene-
sulfonyl moiety at position-1 as in 13a,b did not offer
any advantage. However, incorporating a substituted
carbamoyl counterpart as in 14b (R = Cl) resulted in an
increase in antimicrobial activity against B. subtilis and
E. coli. Whereas, introducing a thiocarbamoyl moiety
at position-1 led to a potentially active compound 15a
(R = H) which exhibited 50ꢀ of the activity of Ampicillin
against S. aureus, B. subtilis and E. coli, however with no
antifungal efficacy.
Shifting to the second series of pyridines 17–23
illustrated in Scheme 3, the key intermediate
sulphonamide 17 showed mild activities only against
the Gram positive S. aureus and B. subtilis (MIC 50
and 100 µg/mL, respectively). Condensation of the
1
N -sulfonamido group with different aryl and hetaryl
aldehydes resulted into two active azomethines 18b,c,
among which the analog 18b (R = 4-Cl-C H ) showed
Conclusion
6
4
e results revealed that twenty six out of the tested fifty
better activity than 18c (R = 2-thienyl), against S. aureus
and B. subtilis which was 50ꢀ of that of Ampicillin, and
E. coli. It has also exhibited a remarkable antifungal
activity against C. albicans which was 25ꢀ of that of
Clotrimazole. However, cyclization into a thiazolidine
ring as in 19c (R = 2-thienyl) led to a decrease in the Gram
positive efficacy and a two-fold increase in the activity
against Gram negative organisms when compared to the
parent 18c. Furthermore, derivatization of the parent
sulphonamide 17 into sulfonylureido function gave rise
to a moderately active compound 20c (R = 4-Cl-C H )
eight compounds displayed variable inhibitory effects on
the growth of the tested Gram positive and Gram negative
bacterial strains. In general, most of the tested compounds
revealed better activity against the Gram positive than the
Gram negative bacteria. Among the Gram positive bac-
teria tested, two strains namely; S. aureus and B. subtilis
showed high sensitivity towards the tested compounds.
However, most of the active compounds displayed better
antibacterial activity against E. coli when compared with
P. aeruginosa and K. pneumoniae. Moreover, eleven com-
pounds were able to produce appreciable growth inhibi-
tory activity against C. albicans fungus when compared
with Clotrimazole. However, all of the tested compounds
lacked antifungal activity against A. niger.
6
4
with MIC range of 50–100 µg/mL. However, bioisosteric
replacement of the sulfonylureido function with a
sulfonylthioureido as in 21a–d resulted in a remarkable
improvement in the antimicrobial profile. Among these,
the analog 21d (R = 4-F-C H ) exhibited an improvement
6
4
in the antibacterial potentials against both Gram positive
and Gram negative organisms (B. subtilis and E. coli)
together with an appreciable antifungal activity against C.
albicans (25ꢀ of the activity of Clotrimazole). Cyclization
of the former sulfonylthioureido compounds into
thiazolidine derivatives (22a–d) resulted in a remarkable
enhancement in the overall antimicrobial potential.
Among these, compound 22d (R = 4-F-C H ) proved to be
equipotent to Ampicillin against S. aureus, E. coli and B.
subtilis (MIC values 6.25, 6.25 and 12.5 µg/mL), and 50ꢀ
of its activity against M. luteus and P. aeruginosa (MIC 25
µg/mL), together with a remarkable antifungal activity
against C. albicans (MIC 25 µg/mL) which represents
Acknowledgements
e authors are very grateful to the authorities of the
Institute of Research and Consultation, King Abdulaziz
University, Jeddah, Saudi Arabia, as well as SABIC
group of companies, for the financial support of this
research. Extendable thanks are due to the staff mem-
bers of the Department of Health and Human Services,
National Cancer Institute (NCI), Bethesda, Maryland,
U.S.A. for carrying out the anticancer screening of the
newly synthesized compounds.
6
4
Declaration of interest
5
0ꢀ of that of Clotrimazole. Finally, cyclization of
the sulfonylthioureido function into thiazolines 23d
e authors report no conflicts of interest.