Synthesis and antimicrobial studies of chalconyl pregnenolones

Article abstract of DOI:10.1016/j.steroids.2011.07.001

An efficient and facile synthesis of 17-chalconyl derivatives of pregnenolone and their evaluation as antimicrobial agents against various microbial strains is reported. The scheme involves the transformation of the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to the corresponding chalcone derivatives. The compounds 3a-3j showed significant antimicrobial activity against all microbial strains used for testing.

Full text of DOI:10.1016/j.steroids.2011.07.001

Steroids 76 (2011) 1358–1362
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Steroids
journal homepage: www.elsevier.com/locate/steroids
Synthesis and antimicrobial studies of chalconyl pregnenolones
b
c
Abid H. Banday a, , M. Iqbal Zargar , Bashir A. Ganaie
⇑
a Department of Chemistry, Islamia College of Science and Commerce, Srinagar, 190009 J&K, India
b Department of Pharmaceutical Sciences, University of Kashmir, Srinagar, 190009 J&K, India
c Department of Biochemistry, University of Kashmir, Srinagar, 190009 J&K, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and facile synthesis of 17-chalconyl derivatives of pregnenolone and their evaluation as anti-
microbial agents against various microbial strains is reported. The scheme involves the transformation of
the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to the corresponding
chalcone derivatives. The compounds 3a–3j showed significant antimicrobial activity against all micro-
bial strains used for testing.
Received 16 April 2011
Received in revised form 29 June 2011
Accepted 2 July 2011
Available online 13 July 2011
Ó 2011 Elsevier Inc. All rights reserved.
Keywords:
Chalcone
Pregnenolone
TLC
Antimicrobials
Microbial strains
1. Introduction
we, in continuation of our programme on the synthesis of D-ring
substituted steroidal analogs, aimed to investigate the synthesis
Steroids have been the prime focus of research throughout the
scientific history. But the recent past has seen an exhaustive focus
of research being diverted towards these biologically important
molecules. This is pertinently true of the rational semi synthetic
modifications of steroidal molecules. Probably, it is because of
the various advantages associated with steroid based chemothera-
peutics. These compounds turn out to be non-toxic, less vulnerable
to multi-drug resistance (MDR) and highly bioavailable because of
being capable of penetrating the cell wall. Although various
modifications of steroids including derivatization, cyclization, het-
erocyclization etc. have been tried but as far the literature prece-
dents are concerned, little efforts have been made towards the
efficient synthesis and simultaneous biological analysis of steroid
based chalcone derivatives. This is pertinently important because
chalcone moieties are common substructures in numerous natural
products belonging to the flavonoid family [1–4]. Chalcone deriva-
tives are very versatile as physiologically active compounds and
substrates for the evaluation of various organic syntheses. These
compounds have been reported to possess several biological activ-
ities, such as cytotoxic [5–8] antimalarial [9,10], antileishmanial
[11,12], anti-inflammatory [13,14], anti-HIV [15], antifungal [16]
and as tyrosine kinase inhibitors [17]. There are also few recent
reports about some similar steroidal analogs acting as good antimi-
crobial agents [18]. Having such varied pharmacological activities,
of steroidal chalcone derivatives starting from readily available
20-keto pregnenanes [19]. Although the chemistry is already
known [20], we efficiently synthesized various such chalcone
derivatives including few novel ones and studied their antimicro-
bial properties which we wish to report herein.
2. Experimental
2.1. General methods
Melting points were recorded on Buchi melting point apparatus
D-545; IR spectra (KBr discs) were recorded on Bruker Vector 22
instrument. NMR spectra were recorded on Bruker DPX200 instru-
ment in CDCl3 with TMS as internal standard for protons and sol-
vent signals as internal standard for carbon spectra. Chemical
shift values are mentioned in d (ppm) and coupling constants are
given in Hz. Mass spectra were recorded on EIMS (Shimadzu)
and ESI-esquire 3000 Bruker Daltonics instrument. The progress
of all reactions was monitored by TLC on 2 Â 5 cm pre-coated silica
gel 60 F254 plates of thickness of 0.25 mm (Merck). The chromato-
grams were visualized under UV 254–366 nm and iodine.
2.2. Chemical synthesis
2.2.1. General procedure for the synthesis of chalconyl derivatives
To a solution of pregnenolone 1 (0.316 g, 1 mmol, 1 eq.) in eth-
anol (10 ml) was added a conc. aq. solution of KOH (2 eq.). Then
⇑
Corresponding author. Fax: +91 194 2429014.
E-mail address: abidrrl@gmail.com (A.H. Banday).
0039-128X/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.steroids.2011.07.001

A.H. Banday et al. / Steroids 76 (2011) 1358–1362
1359
Table 1
aldehyde 2 (1.2 eq.) was charged into the reaction mixture to get
Nature of group ‘‘R’’ in the compounds 3a–3j.
the corresponding benzylidine derivative 3 (Scheme 1). After com-
pletion as revealed by thin layer chromatography (TLC) in an aver-
age span of around 1 h, the reaction mixture was precipitated using
water because of the limited solubility. The precipitate was fil-
tered, dried and monitored through TLC for the purity. Thin layer
chromatography revealed just a single spot which proved the pres-
ence of a single product. For further purification, the product was
recrystallized from EtOAc:Hexane to give product as solid white
powder. It is to be mentioned that when non-aromatic aldehydes
were used, the product was formed in a very minor quantity and
that too not stable enough at ambient conditions. Thus the study
was restricted to the use of aromatic aldehydes only. The spectral
data of various compounds (Table 1) is given as under (Most of the
peaks due to steroidal skelton were merged and could not be dif-
ferentiated in the 1H NMR. Thus d values of only those peaks that
distinguish the product and could easily be differentiated are re-
ported as under):
Entry
3a
Nature of R
Entry
3f
Nature of R
F
3b
3c
3g
3h
OMe
MeO
3d
3e
3i
3j
Br
F
O
2.2.1.1. (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-
decahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenan-
J = 8.73,1 H); 3.54 (m, 1H), 5.36 (s, 1H), 6.75 (d, J = 15.93, 1H),
7.27 (m, 4H), 7.51 (d, J = 15.93, 1H); 13C NMR (500 MHz, CDCl3):
d 12.36, 19.38, 20.13, 20.48, 21.78, 24.10, 30.62, 30.86, 31.03,
35.54, 36.27, 38.14, 43.26, 43.96, 49.11, 56.21, 60.99, 71.73,
120.44, 124.94, 127.29, 128.65, 131.18, 139.63, 140.54, 198.42;
ESI-MS: 441 (M+Na); Anal. Calcd. for C29H38O2: C, 83.21; H, 9.15;
Found C, 83.03; H, 9.33.
thren-17(b)-yl)-3-phenylprop-2-en-1-one
(3a). White
powder
(86%). M.p: 128–131 °C; IR (KBr) cmÀ1: 3425, 2938, 1804, 1637,
1403, 1041, 689; 1H NMR (CDCl3): d 0.63 (s, 3H), 1.00 (s, 3H),
1.61–1.90 (m, 6H), 2.20–2.38 (m, 3H), 2.82 (t, J = 8.80, 1H); 3.51
(m, 1H); 6.78 (s, J = 16.00, 1H), 7.39 (m, 3H), 7.55 (m, 3H); 13C
NMR (500 MHz, CDCl3): d 13.33, 19.26, 21.07, 22.67, 24.62, 31.13,
31.78, 31.99, 37.22, 41.81, 45.11, 48.61, 48.78, 48.95, 49.12,
49.29, 50.04, 57.14, 61.97, 71.22, 121.24, 126.69, 128.29, 128.90,
130.41, 134.62, 140.85, 141.96, 201.32; ESI-MS: 405 (M+H); Anal.
Calcd. for C28H36O2: C, 83.12; H, 8.97; Found C, 83.37; H, 8.83.
2.2.1.4. (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-
decahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenan-
thren-17(b)-yl)-3-p-tolylprop-2-en-1-one
(3d). Solid
yellowish
powder (78%). M.p: 243–245 °C; IR (KBr) cmÀ1: 3397, 2941,
1804, 1773, 1637, 1403, 1216, 1039, 758; 1H NMR (CDCl3): d 0.63
(s, 3 H), 1.00 (s, 3H), 1.61–1.90 (m, 6H), 2.20–2.38 (m, 3H), 2.45
(s, 3H), 2.85 (t, J = 8.43, 1H); 3.52 (m, 1H), 5.36 (s, 1H), 6.74 (d,
J = 15.98, 1H), 7.22 (d, J = 7.82, 2H), 7.48 (d, J = 7.82, 2H), 7.54 (d,
J = 15.98, 1H); 13C NMR (500 MHz, CDCl3): d 12.42, 18.38, 20.13,
20.48, 21.78, 23.70, 30.62, 30.86, 31.03, 35.54, 36.27, 38.14,
41.27, 43.96, 49.11, 56.21, 60.99, 70.73, 120.44, 124.94, 127.29,
128.65, 131.08, 139.73, 140.55, 199.42; ESI-MS: 441 (M+Na); Anal.
Calcd. for C29H38O2: C, 83.21; H, 9.15; Found C, 83.31; H, 8.95.
2.2.1.2. (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-
decahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenan-
thren-17(b)-yl)-3-o-tolylprop-2-en-1-one
(3b). Yellow
powder
(89%). M.p: 208–210 °C; IR (KBr) cmÀ1: 3405, 2941, 1774, 1674,
1403, 1041, 757; 1H NMR (CDCl3): d 0.62 (s, 3H), 1.00 (s, 3H),
1.63–1.90 (m, 6H), 2.22–2.35 (m, 3H), 2.38 (s, 3H), 2.82 (t,
J = 8.43, 1H); 3.52 (m, 1H), 5.32 (s, 1H), 6.69 (d, J = 15.78, 1H),
7.32 (m, 3H), 7.57 (d, J = 6.83, 1H), 7.82 (d, J = 15.78,1H); 13C
NMR (500 MHz, CDCl3): d 13.54, 19.46, 19.95, 21.21, 22.84, 24.77,
31.67, 31.92, 32.09, 36.61, 37.27, 37.42, 39.32,42.32, 45.00, 50.13,
57.25, 62.17, 71.70, 71.76, 121.48, 121.72, 126.29, 126.37, 128.01,
129.10, 130.08, 130.93, 133.81, 138.27, 139.06, 140.53, 140.86,
200.51; ESI-MS: 441 (M+Na); Anal. Calcd. for C29H38O2: C, 83.21;
H, 9.15; Found C, 83.32; H, 8.83.
2.2.1.5. (2E)-3-(3-fluorophenyl)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,
14,15,16,17-tetradecahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclo-
penta[a]phenanthren-17(b)-yl) prop-2-en-1-one (3e). Solid yellow-
ish powder (84%). M.p: 228–231 °C; IR (KBr) cmÀ1: 3407, 2940,
1773, 1678, 1508, 1232, 1040, 756; 1H NMR (CDCl3): d 0.62 (s,
3H), 1.00 (s, 3H), 1.61–1.90 (m, 6H), 2.20–2.32 (m, 3H), 2.84 (t,
J = 8.92, 1H); 3.52 (m, 1H), 5.36 (s, 1H), 6.70 (d, J = 15.93, 1H),
7.08 (m, 2H), 7.53 (m, 3H); 13C NMR (500 MHz, CDCl3): d 13.06,
19.28, 20.13, 20.48, 21.78, 25.10, 30.62, 30.86, 31.03, 35.54,
36.27, 38.14, 43.26, 43.96, 49.11, 56.21, 60.99, 71.73, 122.44,
124.94, 126.49, 129.02, 132.18, 139.63, 140.53, 196.92; ESI-MS:
2.2.1.3. (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-
decahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenan-
thren-17(b)-yl)-3-m-tolylprop-2-en-1-one (3c). Solid white powder
(85%). M.p: 211–213 °C; IR (KBr) cmÀ1: 3415, 2934, 1804, 1773,
1638, 1403, 1042, 779; 1H NMR (CDCl3): d 0.63 (s, 3H), 1.00 (s,
3H), 1.61–1.90 (m, 6H), 2.20–2.34 (m, 3H), 2.44 (s, 3H), 2.86 (t,
R
O
O
OHC
R
2
EtOH/ KOH
HO
HO
3
1
Scheme 1. Synthesis of D-ring substituted steroidal chalcones.

1360
A.H. Banday et al. / Steroids 76 (2011) 1358–1362
445 (M+Na); Anal. Calcd. for C28H35F O2: C, 79.58; H, 8.35, F, 4.50;
Found C, 79.62; H, 8.52, F, 4.32.
needles (88%). M.p:111–113 °C; IR (KBr) cmÀ1: 3395, 2939, 2872,
1673, 1605, 1551, 1200, 754; 1H NMR (CDCl3): d 0.61 (s, 3H),
1.03 (s, 3H), 1.65–1.90 (m, 6H), 2.20–2.30 (m, 3H), 2.78 (t,
J = 8.68, 1H), 3.52 (m, 1H), 5.35 (s, 1H), 6.48 (d, J = 15.46, 1H),
6.65–6.69 (dd, J = 3.68, 2H), 7.27 (m,1H), 7.48 (s, J = 15.46, 1H);
13C NMR (500 MHz, CDCl3): d 123.26, 19.28, 21.14, 20.48, 21.78,
24.10, 30.62, 30.86, 31.03, 35.54, 37.25, 38.14, 43.26, 43.96,
49.11, 56.21, 60.99, 71.73, 120.44, 124.94, 127.29, 128.65, 132.19,
136.95, 142.14, 197.44; ESI-MS: 484 (M+H); Anal. Calcd. for
2.2.1.6. (2E)-3-(4-fluorophenyl)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,
14,15,16,17-tetradecahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclo-
penta[a]phenanthren-17(b)-yl) prop-2-en-1-one (3f). Solid white
powder (80%). M.p:196–198 °C; IR (KBr) cmÀ1: 3417, 2946, 1772,
1678, 1508, 1232, 1045, 755; 1H NMR (CDCl3): d 0.62 (s, 3H),
1.00 (s, 3H), 1.61–1.90 (m, 6H), 2.20–2.33 (m, 3H), 2.83 (t,
J = 8.61,1 H), 3.63 (m, 1H), 5.37 (s, 1H), 6.75 (d, J = 15.84, 1H),
7.08 (m, 2H), 7.24–7.32 (m, 2H), 7.50 (d, J = 15.84, 1H); 13C NMR
(500 MHz, CDCl3): d 12.22, 19.26, 20.43, 20.48, 21.78, 23.15,
30.62, 30.86, 31.03, 35.54, 36.27, 38.14, 43.26, 43.96, 49.11,
56.21, 60.99, 71.73, 120.52, 124.94, 127.29, 128.65, 131.18,
139.63, 140.54, 196.12; ESI-MS: 445 (M+Na); Anal. Calcd. for
C
26H34O3: C, 79.15; H, 8.69; Found C, 79.32; H, 8.82.
2.3. Biology
The bacterial strains used for the analysis were Bacillus subtilis
(MTCC 619), Staphylococcus epidermidis (MTCC 435), Proteus vulga-
ris (MTCC 426) and Pseudomonas aeruiginosa (MTCC 424). The fun-
gal strains used were Aspergillus niger (MTCC 1344) and Penicillium
chrysogenum (MTCC 947). All the bacterial and fungal strains were
obtained from The Microbial Type Culture Collection and Gene
Bank (MTCC), Institute of Microbial Technology (IMTECH), Chandi-
garh, India. Kenamycin and flucanazole were used as standard anti-
bacterial and antifungal substances respectively, under similar
conditions for comparison. Dimethyl sulphoxide (DMSO) was used
as negative control.
The test organisms were cultured on agar slants, incubated 24 h
at 37 0.5 °C and 24–48 h at 27 0.2 °C for bacteria and fungi
respectively to get the freshly prepared cultures. The steroidal
derivatives were evaluated for antimicrobial activity against these
freshly prepared strains of test organisms by agar diffusion method
[21]. Muller Hinton Agar (MHA) and Potato Dextrose Agar (PDA)
were used as nutrient media for bacterial and fungal strains
respectively. The media (MHA and PDA) was prepared using dis-
tilled water and 20 ml of it was transferred into 50 ml test tubes,
the test tubes were tightly plugged with cotton and sterilized in
autoclave at 15 lb/in2 for 15 min as directed by the manufacturer.
After Sterilization the medium was inoculated with freshly cul-
tured bacterial strains under sterile condition i.e. under Laminar
Flow. The inoculation was done when the temperature of the med-
ium reached to 50–40 °C, so that test organism may not die at
higher temperature. The medium inoculated with test microorgan-
isms was transferred into the plates of 90 mm size under sterile
conditions. The medium was allowed to solidify and the wells (4/
C28H35F O2: C, 79.58; H, 8.35, F, 4.50; Found C, 79.42; H, 8.52, F,
4.67.
2.2.1.7. (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-
decahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenan-
thren-17(b)-yl)-3-(4-methoxy phenyl)prop-2-en-1-one (3g). Solid
white powder (87%). M.p: 200–203 °C; IR (KBr) cmÀ1: 3415,
2926, 2853, 1803, 1708, 1637, 1508, 1255, 1036, 762; 1H NMR
(CDCl3): d 0.60 (s, 3H), 1.00 (s, 3H), 1.65–1.90 (m, 6H), 2.20–2.36
(m, 3H), 2.83 (t, J = 8.89, 1H), 3.53 (m, 1H), 3.87 (s, 3H), 5.36 (s,
1H), 6.65 (d, J = 15.92, 1H), 6.91 (d, J = 8.72, 2H), 7.51 (d, J = 8.72,
2H), 7.53 (d, J = 15.84, 1H); 13C NMR (500 MHz, CDCl3): d 12.13,
18.31, 21.11, 20.48, 21.78, 24.10, 30.62, 30.81, 31.23, 34.52,
36.27, 38.14, 43.26, 43.96, 49.22, 56.21, 60.99, 71.73, 120.44,
124.94, 127.29, 128.65, 133.16, 139.63, 140.54, 196.54; ESI-MS:
457 (M+Na); Anal. Calcd. for C29H38 O3: C, 80.14; H, 8.81; Found
C, 80.32; H, 8.67.
2.2.1.8. (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-
decahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenan-
thren-17(b)-yl)-3-(2-methoxy phenyl)prop-2-en-1-one (3h). Grey
powder (76%). M.p: 225–227 °C; IR (KBr) cmÀ1: 3425, 2940,
1728, 1636, 1598, 1296, 1024, 753; 1H NMR (CDCl3): d 0.63 (s,
3H), 1.00 (s, 3H), 1.65–1.90 (m, 6H), 2.20–2.32 (m, 3H), 2.89 (t,
J = 8.85, 1H), 3.52 (m, 1H), 3.91 (s, 3H), 5.37 (s, 1H), 6.94 (d,
J = 16.16, 1H), 6.98 (m, 2H), 7.36 (m, 1H), 7.55 (d, J = 6.37, 1H),
7.88 (d, J = 16.16, 1H); 13C NMR (500 MHz, CDCl3): d 12.34, 18.34,
20.13, 20.48, 21.78, 25.10, 30.62, 30.86, 31.03, 35.54, 36.27,
38.14, 43.26, 43.96, 49.11, 56.21, 60.99, 71.73, 118.30, 124.94,
127.29, 128.65, 131.18, 139.63, 140.54, 195.23; ESI-MS: 457
(M+Na); Anal. Calcd. for C29H38 O3: C, 80.14; H, 8.81; Found C,
80.02; H, 8.97.
plate) of 6 mm diameter and 50
sterile cork borer. The solution of test compound 1000
prepared in DMSO and the wells bored on the medium were each
filled (50 g) with test compound using micropipette (20–200 l).
ll volume were bored on it using
lg/ml was
l
l
Four wells were bored on the plates and each filled with same
compound and two plates for each test compound were taken
and the experiment was repeated twice. The discs of Kenamycin
and Flucanazole were also incorporated into the medium for com-
2.2.1.9. (2E)-3-(3-bromophenyl)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,
14,15,16,17-tetradecahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclo-
penta[a]phenanthren-17(b)-yl) prop-2-en-1-one (3i). Brown powder
(79%). M.p: 217–219 °C; IR (KBr) cmÀ1: 3435, 2937, 1728, 1641,
1593, 1296, 1024, 763; 1H NMR (CDCl3): d 0.61 (s, 3H), 1.03 (s,
3H), 1.65–1.90 (m, 6H), 2.20–2.34 (m, 3H), 2.56 (t, J = 9.12, 1H),
3.52 (m, 1H), 5.35 (s, 1H), 6.84 (d, J = 15.31, 1H), 6.94–7.15 (m,
4H), 7.24 (d, J = 15.31, 1H); 13C NMR (500 MHz, CDCl3): d 13.03,
19.38, 20.13, 24.14, 21.23, 25.15, 30.62, 30.86, 31.03, 35.54,
36.27, 38.14, 43.26, 44.96, 49.11, 56.21, 60.99, 74.13, 120.44,
124.94, 127.29, 128.65, 131.18, 140.43, 140.54, 196.43; ESI-MS:
484 (M+H); Anal. Calcd. for C28H35BrO2: C, 69.56; H, 7.30, Br,
16.53; Found C, 69.69; H, 7.47; Br, 16.74.
parison (10–30 lg). The plates containing test organism and test
material in contact were incubated at 37 0.5 °C for 24 h. Same
procedure was employed for antifungal activity however, the cul-
ture strains of fungi were maintained on potato dextrose agar
and spores were transferred in the PDA medium and the plates
were incubated at 27 0.2 °C for 24–48 h. Inhibition of growth of
test organisms (bacterial and fungal) in presence of test material
and standard was measured with the help of standard scale and
the mean values of inhibition zones are reported in Table 2.
3. Results and discussion
2.2.1.10.
(2E)-3-(furan-2-yl)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,
Though the importance of different chalcone based natural
product analogs is now well validated, only few efforts have been
reported for their efficient synthesis and biological evaluation as
14,15,16,17-tetradecahydro-3(b)-hydroxy-10,13-dimethyl-1H-cyclo-
penta[a]phenanthren-17(b)-yl) prop-2-en-1-one (3j). Solid white

A.H. Banday et al. / Steroids 76 (2011) 1358–1362
1361
Table 2
Antibacterial and Antifungal screening data of compounds 3a–3j.
Compound
(Zone of inhibition in ‘‘mm’’)
Antibacterial activities
Antifungal activities
B. subtilis (MTCC
S. epidermidis (MTCC
P. Vulgaris (MTCC
P. aeuriginosa (MTCC
A. niger
P. chrysogenum (MTCC
619)
435)
426)
424)
(MTCC1344)
947)
3a
3b
3c
3d
3e
3f
3g
3h
19
17
–
17
16
13
12
10
14
–
12
12
–
10
11
10
–
18
14
13
10
–
10
–
22
–
11
13
12
13
10
–
11
10
13
11
–
–
10
12
10
12
16
19
13
10
17
12
–
12
10
13
10
13
12
11
13
11
–
16
11
11
12
14
10
20
–
3i
3j
Control
Kenamycin
Flucanazole
–
24
–
24
–
17
–
18
–
14
P. vulgaris, Proteus vulgaris; B. subtilis, Bacillus subtilis; S. epidermidis, Staphylococcus epidermidis; P. aeruginosa, Pseudomonas aeruginosa; DMSO – Negative control; well
diameter/vol. – 6 mm/50 l; Kenamycin – standard for antibacterial activity; Flucanazole – standard for anti fungal activity.
l
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far as steroidal modifications are concerned. This specially refers to
the chalconyl derivatives at the D-ring of steroids including the
very important class of pregnanes. Though there are reports for
the synthesis of other such analogs [22], the same is not true
for the chalconyl derivatives at the D-ring. Taking inspiration from
the number of reported biological activities associated with struc-
turally related analogs, we, in continuation of our efforts towards
the synthesis of novel D-ring semisynthetic analogs [19], herein
report a novel efficient and simple synthesis of D-ring chalcone
derivatives of 20-keto pregnenanes and their evaluation as poten-
tial antimicrobial agents. The preparation of the latter involves the
following synthetic approach.
3.1. Biology
The following table gives the antimicrobial screening data ob-
tained after treating different microbial strains with test doses of
the different steroidal chalconyl derivatives and the values are re-
ported in terms of zone of inhibition in ‘‘mm’’.
It is clear from the above data, that all the compounds 3a–3j
showed significant antimicrobial activity against all microbial
strains used for testing. It is evident from the data that even the po-
sition of substituent on the aromatic ring influences the relative
activity which can be attributed to their differences in either the
bioavailability or the protein binding properties.
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J
4. Conclusion
A series of novel D-ring substituted chalconyl derivatives of pre-
gnenolones were synthesized and screened for antimicrobial activ-
ity against a panel of various bacterial and fungal strains. From the
data it was found that most of the compounds are having promis-
ing antimicrobial activity.
Acknowledgement
[18] Keller AC, Maillard MP, Hostettmann K. Antimicrobial steroids from the fungus
Fomitopsis pinicola. Phytochemistry 1996;41:1041–6;
The authors thank Head, Dept. of Chemistry, ICSC for his
encouragement.
Moharebi RA, Hana HY. Synthesis of progesterone heterocyclic derivatives of
potential antimicrobial activity. Acta Pharm 2008;58:29–42.
[19] Banday AH, Mir BP, Lone IH, Suri KA, Kumar HMS. Studies on novel D-ring
substituted steroidal pyrazolines as potential anticancer agents. Steroids
2010;75(12):805–9;
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