Synthesis and biological evaluation of nitrogen-containing benzophenone analogues as TNF-α and IL-6 inhibitors with antioxidant activity

Article abstract of DOI:10.1016/j.bmcl.2010.02.001

A series of nitrogen-containing benzophenone analogues were synthesized by Mannich reaction and evaluated for the inhibition of pro-inflammatory cytokines, TNF-α and IL-6. DPPH (1,1-diphenyl-2-picryl hydrazine) radical scavenging activity and its kinetics were studied to determine the antioxidant potential of the test samples. All the synthesized compounds exhibited promising activity against IL-6 in a range of 81-89%, 09-42% at 10 and 1 μM, respectively, concentration. Exceptionally, the compound 20e was observed to be an effective inhibitor of TNF-α (54%) and IL-6 (97%), (47%) at 10 and 1 μM concentrations with minimum toxicity (22%) against CCK-8 cells. With few exceptions, all other compounds were found to be excellent inhibitors of IL-6 and moderate to excellent inhibitors of TNF-α, however the toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the tested compounds, 16a, 17g, 18f, 18g, 19g and 20e were found to possess significant antioxidant activity.

Full text of DOI:10.1016/j.bmcl.2010.02.001

Bioorganic & Medicinal Chemistry Letters 20 (2010) 2292–2296
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Synthesis and biological evaluation of nitrogen-containing benzophenone
analogues as TNF-
a
and IL-6 inhibitors with antioxidant activity
b
b
b
c
Babasaheb P. Bandgar a,b, , Sachin A. Patil , Jalinder V. Totre , Balaji L. Korbad , Rajesh N. Gacche ,
*
Baliram S. Hote b, Shivkumar S. Jalde b, Hemant V. Chavan a
a Organic Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, India
b Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, India
c School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded 431 606, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of nitrogen-containing benzophenone analogues were synthesized by Mannich reaction and
Received 25 August 2009
Revised 30 December 2009
Accepted 1 February 2010
Available online 13 February 2010
evaluated for the inhibition of pro-inflammatory cytokines, TNF-a and IL-6. DPPH (1,1-diphenyl-2-picryl
hydrazine) radical scavenging activity and its kinetics were studied to determine the antioxidant poten-
tial of the test samples. All the synthesized compounds exhibited promising activity against IL-6 in a
range of 81–89%, 09–42% at 10 and 1
20e was observed to be an effective inhibitor of TNF-
centrations with minimum toxicity (22%) against CCK-8 cells. With few exceptions, all other compounds
were found to be excellent inhibitors of IL-6 and moderate to excellent inhibitors of TNF- , however the
lM, respectively, concentration. Exceptionally, the compound
a
(54%) and IL-6 (97%), (47%) at 10 and 1 M con-
l
Keywords:
Nitrogen-containing benzophenone
Anti-inflammatory
a
toxicity profiles of these compounds need to be ameliorated in further optimization studies. Amongst the
tested compounds, 16a, 17g, 18f, 18g, 19g and 20e were found to possess significant antioxidant activity.
Ó 2010 Elsevier Ltd. All rights reserved.
TNF-a
IL-6
Antioxidant activity
Inflammation is a multi-step and complex biological reaction
involving variety of pro-inflammatory cellular proteins, enzymes
and cytokines. The pro-inflammatory cytokines, interleukin-6 (IL-
man include biologics directed towards these cytokines such as
adalimumab (Humira), etanercept (Enbrel) and infliximab
(Remicade) which have demonstrated a significant efficacy in the
treatment and management of RA.12 However, these agents require
administration via injection or infusion, therefore identification of
an orally available small molecule therapy would provide an addi-
tional benefit to the patients. In spite of enormous efforts, no small
6) and tumour necrosis factor-a (TNF-a) are implicated in the
pathogenesis of various inflammatory disorders such as rheuma-
toid arthritis (RA), inflammatory bowel disease, osteoarthritis, pso-
riasis, endotoxemia and/or toxic shock syndrome.1–9 Apart from
pro-inflammatory attributes these cytokines have a wide array of
functions for maintaining the normal cellular physiology. For
molecule has yet been approved to specifically inhibit TNF-
ity. Therefore, there is a continuing interest in the search of small
molecules that can block TNF- signalling without side effects
a activ-
example, TNF-
such as IL-1, IL-6 and IL-10; it can also activate T cells and other
inflammatory cells. However, an overabundance of TNF- and IL-
a
can induce apoptosis and secretion of cytokines
a
and general disadvantages associated with protein drugs.
Amongst the pro-inflammatory cytokines, the IL-6 is a pleiotro-
pic cytokine, that is, abundant in both the synovium and serum of
RA patients and induces a broad range of cellular and physiological
responses during the inflammation reaction. In addition to playing
a role in inflammation and hematopoiesis, it is involved in other
processes such as neuronal differentiation and bone loss. IL-6 is
produced at the site of inflammation and plays a key role in acute
phase response. IL-6 is a central regulator of inflammatory dis-
eases, including end-stage renal disease and rheumatoid arthri-
tis.13 Till-date, designing the IL-6 inhibitory agents has remained
a significant hope in the mainstream of anti-inflammatory drug
development.
a
6 is attributed to the development of various human ailments
including inflammatory disorders. Targeting the inhibition of cyto-
kines, in particular TNF-
a, has been successful in several clinical
trials for the treatment of RA. Nevertheless, the TNF-
a
inhibition
has been identified as one of the attractive targets for the design
and development of anti-inflammatory agents.10
Upregulation of tumour necrosis factor-alpha (TNF-a) has
several concerns for the onset and progression of a number of dis-
eases such as diabetes, multiple sclerosis, RA, psoriatic arthritis,
cachexia, sepsis, tumourigenesis and inflammatory bowel
diseases.11 Therapies that have successfully targeted TNF-
a in
Benzophenones, the precursors for the synthesis of the title
compounds are essential due to their diverse biological and
chemical properties. In recent years a vast body of literature has
* Corresponding author.
E-mail address: bandgar_bp@yahoo.com (B.P. Bandgar).
0960-894X/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2010.02.001

B. P. Bandgar et al. / Bioorg. Med. Chem. Lett. 20 (2010) 2292–2296
2293
CH3
N
O
O
O
HO
N
O
NH
N
COOH
CO2H
H3C
O
N
Cl
H
3
4
2
1
OCH3
CH3
O
O
N
N
CH3
O
Cl
N
Cl
N
O
OCH3
O
N
H
S
NH2
Cl
F
7
5
6
O
OH
Cl
O
N
N
H3C
H
O
N
H3CO
Cl
O
H3CO
NH2
CH3
Cl
10
9
8
N
NH
OH
N
H3CO
H3CO
F
F
O
O
O
N
+
N
H
N
N
O
H
13
11
12
F
F
Figure 1. Some biologically active benzophenones containing nitrogen analogues.
accumulated, linking the therapeutic applications of benzophenon-
es. The suitability of benzophenone analogues (Fig. 1) (1) as chemo-
therapeutic agents, especially as anti-inflammatory, is well
cited.14,15 Several research groups have synthesized benzophenone
analogues (2, 3, 4, 5) and reported as potent anti-inflammatory
agents.16–18 Venu et al. reported benzophenone pyrimidine ana-
logue (6) as an anti-inflammatory agent.19 Ottosen et al. have re-
ported aminobenzophenones, which are novel class of p38 MAP
kinase inhibitors (7) having high anti-inflammatory activity.20 Kha-
num et al. identified benzophenone N-ethyl piperidine ether ana-
logues21 (8) and benzophenone22 analogues (9) as anti-
inflammatory agents. Murari et al. reported benzophenone oxime
analogues (10) as inhibitors of phospholipase A2 with anti-inflam-
matory activity.23 Revesz et al. described benzoylpyridines and
modifications.26 Condensation of 16a–b with various secondary
amines and formaldehyde in the presence of hydrochloric acid in
isopropanol furnished desired derivatives 17e–h, 18e–h, 19e–h
and 20e–h.27
The synthesized compounds 16a–b28, 17e–h, 18e–h, 19e–h
and 20e–h29 were characterized by IR, 1H NMR and mass
spectrophotometer.
The synthesized nitrogen-containing benzophenone was as-
sayed for its biological activities against the pro-inflammatory
cytokines TNF-
a
and IL-630 and antioxidant activity.31 The DPPH
radical scavenging activity and its kinetics were performed in order
to determine the antioxidant potential.32 DPPH is a stable nitro-
gen-centred free radical. Its reaction rates correlate directly with
antioxidant activity; the higher the rate, the more effective the
antioxidant.33 The summary of reduction of DPPH (%) is shown in
Table 1, while the results of the kinetics (%) of DPPH radical scav-
enging activity are summarized in Table 2.
benzophenones (11, 12) as p38
a MAP kinase inhibitors with oral
activity.24 Compound 13 was reported as an inhibitor of secretory
phospholipase A2 with anti-inflammatory activity.25 Based on these
interesting biological activity profiles of benzophenone analogues,
we inspired and made an attempt to synthesize a series of nitro-
Result and discussion: All the synthesized compounds were eval-
uated as inhibitors of TNF-
cent inhibition activity of TNF-
at 10 M concentration. Dexamethasone (1
erence compound. Benzophenone analogues 16a–d have shown
inhibition of TNF- in a range of 11–47%, at 10 M. Nitrogen-con-
taining benzophenone analogues 17e–h, 18e–h, 19e–h and 20e–h
exhibited 20–100% inhibition of TNF- at 10 M. Amongst the ser-
ies 18e, 19f, 19g, 19h and 20e were found to be good to excellent
TNF- inhibitors.
a
and IL-6 at 10
and IL-6 is summarized in Table 1
M) was used as a ref-
lM concentration. Per-
gen-containing benzophenone analogues as inhibitors of TNF-
and IL-6 and as antioxidant agents.
a
a
l
l
Chemicals were purchased from Aldrich Chemical Co. USA. TLC
was performed on an aluminium-backed silica plate with visuali-
zation by UV-light. Melting points were determined with a digital
thermometer. IR spectra were recorded on a FT-IR Shimadzu 8300
spectrophotometer and 1H NMR spectra were recorded on a Bruker
300 MHz spectrometer in CDCl3 using tetramethylsilane as an
internal standard and chemical shifts are reported in d units. Mass
spectra were obtained with a Shimadzu LCMS-2010EV.
Nitrogen-containing benzophenones 16a–b, 17e–h, 18e–h,
19e–h and 20e–h were synthesized as shown in Scheme 1. 2-Hy-
droxy-4,6-dimethoxybenzophenones 16a–b were synthesized fol-
lowing the method described in the literature with minor
a
l
a
l
a
Interestingly, all the synthesized benzophenones were observed
to be promising leads, possessing excellent IL-6 inhibitory activity
as compared to Dexamethasone. Benzophenone analogues 16a–d
showed 71–81% and 09–40% inhibition of IL-6 at 10 and 1.0 lM,
respectively, concentration. Compounds 17e–h, 18e–h, 19e–h
and 20e–h showed 83–100% and 09–57% excellent inhibition of

2294
B. P. Bandgar et al. / Bioorg. Med. Chem. Lett. 20 (2010) 2292–2296
O
O
O
O
F
O
O
B
Cl
A
+
R
O
OH
O
OH
O
O
R
16a-d
15a-d
14
NR1R2
B
17e - h
B
B
O
O
Cl
O
O
F
O
OH
O
O
Br
NR1R2
O
OH
18e - h
NR1R2
O
OH
20e - h
NR1R2
19e - h
R = a) 2-F, b) 3-Cl, c) 2-Br, d) 3-F
NR1R2
=
f)
g)
HN
HN
N
e)
h)
HN
O
HN
Scheme 1. Reagents and conditions: (A) anhyd AlCl3, dry ether, 0 °C, rt to 48 h, 60%; (B) secondary amine, 37% HCHO, isopropanol, HCl reflux, 50–60%.
IL-6 at 10 and 1.0
pounds exhibited toxicity in a range of 34–49% at 10
compounds 16a, 18e, 19f, 19g and 19h and were found to be highly
active and toxic (53–84% at 10 M) in nature.
While discussing the structure–activity relationship, the 3-Cl and
3-F substitution with N-methyl piperazine/pyrrolidine (18e, 20e,
20h, 19g, 19h, etc.) seems to be compatible for the inhibition of IL-
l
M, respectively, concentration. Mostly, all com-
are shown in Table 1. From the results it clearly indicated that sub-
stitution at 30 position (3-Cl, 33–54% and 3-F, 30–47%) is more
favourable for the inhibition of Il-6, while substitution at 20 position
(2-F, 15–21% and 2-Br, 9–22%) is not favourable for the inhibition of
IL-6, however the same cannot hold true for other compounds dem-
onstrating significant IL-6 inhibition. It has been also observed that
the toxicity concerns were found to be more extreme with 3-Cl
and 2-Br substitutions as compared to those with fluoro substitution
at 20 and 30. It is indeed difficult to attribute the structure–activity
lM, except
l
6 (10 lM). To explain in detail the structure–activity relationships,
we have evaluated the activity at 1
l
M concentration and the results
Table 1
Table 2
TNF-
a
and IL-6 inhibitory activities (%) and DPPH (%) radical scavenging activity of N-
Kinetics of the DPPH radical scavenging activity (%) of N-containing benzophenone
containing benzophenone analogues
analogues at 1
lM concentration
Entry
TNF-a
IL-6
Toxicity
DPPH (%)
Entry
DPPH (%)
Time in min
10
l
M
1 lM
2
4
6
8
10
16a
16b
16c
16d
17e
17f
17g
17h
18e
18f
18g
18h
19e
19f
19g
19h
20e
20f
47
00
11
00
19
27
00
10
100
01
11
37
20
65
78
99
54
21
00
01
73
ND
71
78
72
81
83
89
84
87
100
83
83
81
81
97
98
100
97
86
87
93
84
ND
11
31
07
38
21
19
18
15
54
42
33
41
09
19
22
19
47
35
30
34
53
49
43
24
40
39
31
27
77
39
31
53
23
66
61
84
22
42
27
34
00
ND
32.35
16.45
NR
16a
16b
16c
16d
17e
17f
17g
17h
18e
18f
18g
18h
19e
19f
19g
19h
20e
20f
8.20
3.21
NR
12.52
3.90
NR
13.55
4.20
NR
16.83
6.52
NR
18.86
7.60
NR
NR
17.53
19.68
73.31
24.80
NR
33.43
45.29
5.13
13.48
6.23
64.43
NR
40.44
NR
24.70
7.29
00
NR
NR
NR
NR
NR
3.30
3.50
13.68
3.60
NR
5.52
9.20
0.5
3.20
0.8
10.80
NR
9.50
NR
4.20
0.92
18.23
3.95
4.20
16.88
4.24
NR
6.44
11.40
1.60
3.95
1.20
14.15
NR
15.80
NR
5.98
4.51
22.68
4.00
4.74
22.98
6.45
NR
9.45
14.80
1.82
4.50
1.90
17.70
NR
18.50
NR
9.25
2.11
19.45
5.40
6.80
28.92
9.50
NR
14.56
20.95
2.10
6.80
2.11
25.45
NR
19.45
NR
11.75
3.78
38.42
6.20
8.21
34.64
11.90
NR
15.94
22.82
2.11
7.59
2.95
32.50
NR
22.58
NR
13.66
4.78
46.90
20g
20h
DMS (1
20g
20h
GA (1
lM)
l
M)
GA (1 mM)
ND
90.83
The results summarized are the mean values of n = 2, DMS = dexamethasone,
The results summarized are the mean values of n = 2, NR = no reaction, GA = gallic
GA = gallic acid, ND = not determined, NR = not reactive.
acid.

B. P. Bandgar et al. / Bioorg. Med. Chem. Lett. 20 (2010) 2292–2296
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relationship in the case of TNF-
with (18g, 20g) and without (16b, 16d) N-methyl substitution were
found to be nonreactive with TNF- . In general it can be summarized
that the effective inhibition of TNF- , IL-6 and severe toxicity seem
to be closely related with 3-Cl and 2-Br N-methylated analogues as
compared to 2-F and 3-F analogues.
The antioxidant potentials have been described to be closely
associated with anti-inflammatory activities. In general pharmaco-
logical notion, compounds possessing reducing abilities can be a
potential candidate for the inhibition of cyclooxygenase, a key en-
zyme implicated in inflammation.34 However, in the present stud-
ies a paradoxical relation was observed with the compounds (18e,
a inhibition because the compounds
a
a
19h) possessing significant TNF-a and IL-6 inhibitory activities but
nonreactive with DPPH. It was also noted that the condensation of
piperidine (17g, 18g and 19g) was found to be more favourable for
the manifestation of DPPH radical scavenging activities. All other
compounds showed moderate DPPH reducing potentials. The ki-
netic study also revealed that the compounds 17g, 18g, 19g and
20e were observed to be more reactive towards DPPH as compared
to all other compounds under study.
26. Ahluwalia, V. K. Intermediates for Organic Synthesis; New Delhi: I.K.
International, 2005. p. 192.
27. Wilds, A. L.; Nowak, R. M.; McCaleb, K. E. Org. Synth. 1963, 4, 281.
28. Compound 16a: Faint yellow compound, mp 122–124 °C: IR: 1622; 1H NMR
(300 MHz, CDCl3): 13.08 (s, 1H), 7.401 (t, 1H, J = 5.8 Hz), 7.372 (t, 1H,
J = 5.8 Hz), 7.185 (d, 1H, J = 4 Hz), 7.02 (d, 1H), 6.12 (d, 1H), 5.86 (d, 1H), 3.84
(s, 3H), 3.44 (s, 3H), MS: 277 [M+1]. Compound 16b: Faint yellow compound,
mp 118–120 °C: IR: 1625; 1H NMR (300 MHz, CDCl3): 12.24 (s, 1H), 7.491–
7.351 (m, 4H), 6.17 (d, 1H), 5.93 d (d, 1H), 3.86 (s, 3H), 3.48 (s, 3H), MS: 293
[M+1]. Compound 16c: Faint yellow compound, mp 138–140 °C: IR: 1634; 1H
NMR (300 MHz, CDCl3): 13.38 (s, 1H), 7.590 (d, 1H, J = 8 Hz), 7.390 (d, 1H,
J = 8 Hz), 7.352 (m, 1H), 7.23 (t, 1H, J = 6 Hz, 4 Hz), 6.17 (d, 1H), 5.86 (d, 1H),
3.91 (s, 3H), 3.45 (s, 3H), MS: 337 [M+1]. Compound 16d: Off white compound,
mp 78–80 °C: IR: 1635; 1H NMR (300 MHz, CDCl3): 12.83 (s, 1H), 7.531–7.395
(m, 4H), 6.13 (d, 1H), 5.84 (d, 1H), 3.89 (s, 3H), 3.77 (s, 3H), MS: 277 [M+1].
29. Compound 17e: Off white compound, mp 142–144 °C: IR: 1618; 1H NMR
(300 MHz, CDCl3): 7.695 (dd, 1H, J = 8 Hz), 7.441(m, 1H), 7.185 (dd, 1H, J = 8 Hz,
7 Hz), 7.035 (m, 1H), 5.971 (s, 1H), 3.840 (s, 3H), 3.720 (s, 2H), 3.645 (s, 3H),
2.595–2.455 (m, 8H), 2.260 (s, 3H), MS: 389 [M+1]. Compound 17h: Off white
compound, mp 146–148 °C: IR: 1652, 1615; 1H N MR (300 MHz, CDCl3): 8.325
(d, 1H, J = 8 Hz), 7.684 (t, 1H, J = 8 Hz, 6 Hz), 7.421 (d, 1H, J = 6 Hz), 7.377 (t, 1H,
J = 6 Hz, 8 Hz), 6.41 (s, 1H), 4.14 (s, 3H), 3.99 (s, 2H), 3.97 (s, 3H), 2.644 (s, 4H),
1.75 (s, 4H), MS: 360 [M+1]. Compound 18e: Yellow sticky compound, IR: 1619;
1H NMR (300 MHz, CDCl3):7.421 (d, 1H, J = 8 Hz), 7.381–7.315 (m, 3H), 5.92 (s,
1H), 3.860 (s, 3H), 3.713 (s, 3H), 3.615 (s, 3H), 2.635–2.417 (m, 8H), 2.33 (s, 3H),
MS: 405 [M+1]. Compound 18f: White Compound, mp 120–122 °C; IR 1679,
1634; 1H NMR (300 MHz, CDCl3): 7.795 (d, 1H, J = 2 Hz), 7.775 (t, 1H, J = 6 Hz),
7.496 (t, 1H, J = 4 Hz), 7.377 (d, 1H, J = 8 Hz), 6.05 (s, 1H), 3.86 (s, 3H), 3.71 (s,
2H), 3,71 (s, 3H), 3.69 (t, 4H), 2.59 (t, 4H), MS: 372 [M+1]. Compound 19e: Off
white compound, mp 78–80 °C; IR 1618; 1H NMR (400 MHz, CDCl3): 7.395 (d,
1H, J = 8 Hz), 7.382–7.25 (m, 3H), 5.89 (s, 1H), 3.87 (s, 3H), 3.695 (s, 2H), 3.585
(s, 3H), 2.61–2.45 (m, 8H), 2.29 (s, 3H), MS: 450 [M+1]. Compound 19f: Yellow
compound, mp132–134 °C; IR: 1619; 1H NMR (400 MHz, CDCl3): 7.550 (d, 1H,
J = 8 Hz), 7.335 (d, 1H, J = 6 Hz), 7.230 (d, 1H, J = 8 Hz), 7.19 (d, 1H, J = 8 Hz),
5.89(s, 1H), 3.88 (s, 3H), 3.72 (t, 4H), 3.66 (s, 2H), 3.48 (s, 3H), 2.57 (t, 4H), MS:
437 [M+1]. Compound 19g:Off white compound, mp 109–111 °C IR: 1618; 1H
NMR (400 MHz, CDCl3): 7. 552 (d, 1H, J = 8 Hz), 7.395 (d, 1H, J = 7.6 Hz), 7.319
(t, 1H, J = 7.2 Hz, 7.6 Hz), 7.220 (t, 1H, J = 7.2 Hz, 8 Hz), 5.908 (s, 1H), 3.842 (s,
3H), 3.649 (s, 2H), 3.557 (s, 3H), 2.509 (s, 4H), 1.578 (t, 6H), MS: 435 [M+1].
Compound 19h: Yellow compound, mp 79–81 °C; IR: 1617; 1H NMR (400 MHz,
CDCl3): 7.552 (d, 1H, J = 8 Hz), 7.312 (t, 1H, J = 7.6 Hz, 4.8 Hz), 7.216 (m, 2H),
5.887 (s, 1H), 3.863 (s, 3H), 3.759 (s, 2H), 3.504 (s, 3H), 2.627 (s, 4H), 1.779 (s,
4H), MS: 420 [M+1]. Compound 20e:Yellow compound, IR: 1613; 1H NMR
(300 MHz, CDCl3): 7.527(d, 1H, J = 8 Hz), 7.338 (d, 1H, J = 7.6 Hz) 7.289 (t, 1H,
J = 7.6 Hz, 2.4 Hz), 7.227 (m, 1H), 5.86 (s, 1H), 3.84 (s, 3H), 3,67 (s, 2H), 3.48 (s,
3H), 2.60 (s, 4H), 2.46 (s, 2H), 2.25 (s, 3H), MS: 389 [M+1]. Compound 20f:
Yellow compound, IR: 1619; 1H NMR (40 MHz, CDCl3): 7.664 (d, 1H, J = 8 Hz),
7.541 (d, 1H, J = 9.6 Hz), 7.396 (m, 1H), 7.226 (ddd, 1H, J = 2.4 Hz, 2.4 Hz,
2.8 Hz), 6.055 (s, 1H), 3.860 (s, 3H), 3.769 (s, 2H), 3.710 (s, 3H), 3.695 (s, 4H),
2.588 (s, 4H), MS: 376 [M+1].
In conclusion, a new series of nitrogen-containing benzophe-
none analogues were synthesized and evaluated for inhibition of
TNF-a and IL-6 along with antioxidant activity. The result of the
present investigations indicates the importance of these new com-
pounds as potential candidates of anti-inflammatory and antioxi-
dant agents. From the activity results of the tested compounds,
20e showed promising activity against TNF-
cytotoxicity and considerable antioxidant activity. The results of
the other compounds as inhibitors of TNF- and IL-6 are certainly
a and IL-6 with less
a
encouraging, but the cytotoxicity of these compounds limits the
therapeutic applications. However, the basic nitrogen-containing
benzophenone moiety can be considered as one of the scaffolds
for the design and development of anti-inflammatory agents tar-
geting TNF-a and IL-6. The importance of the compound 20e can-
not be ignored as it is one of the intermediates in the lead
optimization process.
Acknowledgements
The authors are thankful and acknowledge Mr. Mahesh Namb-
iar and Mrs. Asha Almeida, Piramal Life Sciences Ltd, Mumbai for
screening of the compounds against TNF-
a and IL-6 as well as
Council of Scientific and Industrial Research (CSIR), New Delhi,
[Project No. 01(2023)/05/EMR-II], Government of India, S.A.P.
thanks CSIR for Senior Research Fellowship.
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2296
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