P. K. Ranjith et al. / Bioorg. Med. Chem. Lett. 23 (2013) 5228–5234
5231
moniae (Gram-negative) using ciprofloxacin as reference, by serial
dilution method.43,44 Table 2 displays activity of final compounds
7(a–j), 8(a–j) and 9 in terms of minimum inhibitory concentrations
the oxygen atom of sulfonyl group and hydrogen atom of methy-
lene group). The molecular assembly is formed with the two types
of weak C–HÁ Á ÁO hydrogen bonds (2.51 Å, 131° and 2.53 Å, 169°)
through inversion centre and translational symmetry. Further
(MIC in lg/mL).
Antifungal activity of the synthesized compounds 7(a–j), 8(a–j)
and 9 were assessed in vitro against three representative fungal
species viz., C. albicans, A. flavus and Rhizopus sp. using Amphoter-
icin B as reference, by serial dilution method.45,46 Table 2 displays
activity of final compounds 7(a–j), 8(a–j) and 9 in terms of mini-
C–HÁ Á Á
p
52 (2.77 Å, 141° and 2.75 Å, 139°) stabilizes zigzag molecu-
lar assembly (Fig. 3).
From the obtained results (Table 2), it has been noticed that
the tested compounds exhibited moderate to good inhibition
(4–256 lg/mL in DMSO) against the tested two Gram-negative
mum inhibitory concentrations (MIC in
l
g/mL).
and one Gram-positive bacteria except 8e, 8g, 8i and 8j against
S. aureus, 7g, 8a, 8c, 8f and 8h against E. coli and 7j, 8b, 8g and 8j
against K. pneumoniae. Some of the compounds exhibited signifi-
cant activity against S. aureus as exemplified by compounds 7b–
7e, and 7h. Surprisingly, the inhibitory activity of the compound
7b and 7e against S. aureus, exhibiting MIC value about onefold
times lower than the reference Ciprofloxacin. Similarly, the inhib-
itory activity of the compound 7c, 7d and 7h against E. coli were
found to be same as that of reference. The inhibitory activity of
the compounds 7b and 7e against K. pneumonia exhibiting MIC va-
lue about two fold times and the compounds 7d and 7h exhibiting
MIC value about one fold times lower than the reference Ciproflox-
acin. Investigation of antifungal screening data has shown that few
of the compounds produced considerable and varied results. It is
apparent from the Table 2 compounds 8e, 8g and 8j failed to exert
Based on the encouraging results from the antibacterial screen-
ing, title compounds were further tested for their in vitro antimy-
cobacterial activity against Mycobacterium tuberculosis H37Rv,
Mycobacterium smegmatis (ATCC 19420), Mycobacterium fortuitum
(ATCC 19542) and MDR-TB strains using isoniazid and rifampicin
as standards. The screening results of in vitro antimycobacterial
activity of the final compounds are tabulated in Table 3.
Single crystal X-ray diffraction study was carried out for 7a to
understand the nature of this analogous series of molecules, and
their conformational and molecular assembly. 7a forms colorless
crystal from ethanol solvents by slow evaporation method at room
temperature. Single crystal data of 7a were recollected on CrysAlis
CCD Xcalibur, Eos (Nova), Oxford Diffraction with X-ray generator
operating at 50 kV and 1 mA, using MoK radiation (k = 0.7107
a
Å).47 The structures were solved and refined by using SHELXL97
,
activity against all the three pathogenic strains at MIC 256
lg/mL
48
using the program suite WinGX.49 Thermal ellipsoid plot and pack-
except 7g against C. albicans (for which MIC was noticed 128
l
g/
50
51
ing diagram were generated using ORTEP-3 and MERCURY
,
respec-
mL). Thus against C. albicans and A. flavus, compounds 7h and 7b,
7e, respectively, showed equivalent potency in comparison with
reference Amphotericin B, whilst all other compounds exhibited
tively. All the non hydrogen atoms were located in difference
Fourier maps and were refined anisotropically, and hydrogen
atoms were fixed geometrically and refined isotropically. The crys-
tal structure of 7a is P-1 space group in triclinic space group. Crys-
tallographic information file (CIF-7a, Cambridge Crystallographic
Data center depository number CCDC 931938) is provided as a
Supplementary data file for the detailed crystallographic informa-
tion. Figure 2 provides the thermal ellipsoid plot with atom num-
bering which shows the preferred conformation via C–HÁ Á ÁO
(2.36 Å, 123°) (intra-molecular hydrogen bond involving between
MIC between 16 and 256
8b, 8c, 8e, 8g, 8h and 8j did not exert antifungal activity against
Rhizopus sp up to 256 g/mL, interestingly compounds 7b, 7d, 7e,
and 7h exhibited the same potency (MIC 16 g/mL) compared to
lg/mL. Although compounds 7a, 7g, 7i,
l
l
the reference drug. Further, the preliminary antimycobacterial
screening of the title compounds were carried out at 1, 10 and
100
lg/mL concentrations against three different TB strains and
also against MDR-TB strain. From the result, it was noticed that
Table 2
Antimicrobial activity data of the synthesized compounds 7 (a–j), 8(a–j) and 9
Minimum inhibitory concentration (MIC in
Bacterial strains
l
g/mL)a
Entry
Fungal strains
S. aureus
E. coli
K. pneumoniae
C. albicans
A. flavus
Rhizopus sp.
7a
7b
7c
7d
7e
7f
7g
7h
7i
128
4
8
8
4
128
64
16
128
32
4
4
32
64
>256
4
256
64
>256
64
>256
128
128
>256
256
>256
256
128
128
4
256
4
64
8
4
128
128
8
128
>256
128
>256
256
128
256
256
>256
256
128
>256
128
16
128
16
128
64
16
64
128
8
128
64
>256
128
>256
>256
>256
128
256
128
>256
256
64
64
8
64
32
256
16
128
16
8
16
128
256
32
128
>256
256
64
128
256
>256
>256
>256
>256
256
>256
128
—
128
256
16
64
256
128
128
256
>256
128
256
128
256
>256
128
>256
256
—
7j
128
256
128
64
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
9
Cfn
Am B
64
>256
256
>256
128
>256
>256
64
8
—
—
8
—
—
8
16
a
MIC values were evaluated at concentration ranging between 4 and 256
lg/mL. The figures in the table show the MIC values in
l
g/mL; MIC (lg/mL) = minimum
inhibitory concentration, that is, lowest concentration to completely inhibit bacterial growth.
Ranjith, P. Karuvalam
