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Frontiers in Biology

Front. Biol.    2018, Vol. 13 Issue (6) : 425-451     https://doi.org/10.1007/s11515-018-1512-4
RESEARCH ARTICLE |
Design, molecular docking, synthesis, characterization, biological activity evaluation (against MES model), in-silico biological activity spectrum (PASS analysis), toxicological and predicted oral rat LD50 studies of novel sulphonamide derivatives
Ajeet1(), Arvind Kumar2, Arun K. Mishra1
1. Drug Design Laboratory, School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh, India
2. Department of Pharmaceutical Chemistry, S. D. College of Pharmacy and Vocational Studies, Muzaffarnagar, Uttar Pradesh, India
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Abstract

BACKGROUND: Among the reported potential agents to treat the epilepsy, sulphonamides are important and their significance cannot be ignored. A series of substituted 4-amino-benzene sulfonamides were designed, keeping in view the structural requirement of pharmacophore.

METHODS: Lipinski rule of five has been calculated; failure to Lipinski rule was not observed. Docking was performed through AutoDock Vina. Molecules have been screened out through docking. Compounds were synthesized and characterized through IR, 1HNMR, 13C NMR, Mass and elemental analysis. The anticonvulsant activity of the synthesized compounds was assessed using the Maximal Electroshock Seizure (MES) model. In-silico biological activity spectrum, toxicological studies, predicted oral rats LD50 were performed.

RESULTS: Docking studies showed good interaction with lyase (Oxo-acid) - human carbonic anhydrase-I (1AZM). The in-silico studies proved them to be with good drug-likeness properties, especially 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g). These results revealed that the synthesized compounds (1a-1c, 2a-2q) exhibited promising anticonvulsant effect against MES model for inhibition of Lyase- Human Carbonic Anhydrase-I.

CONCLUSION: After investigating all the results, the compound 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g) is found to be best in the series. A comparatively good activity of compound 2g suggests us that sulphonamide can be leads to further optimization for building potent and chemically diversified anti-convulsant agents.

Keywords anticonvulsant      sulfonamide      docking      in-silico studies     
Corresponding Authors: Ajeet   
Online First Date: 23 August 2018    Issue Date: 30 November 2018
 Cite this article:   
Ajeet,Arvind Kumar,Arun K. Mishra. Design, molecular docking, synthesis, characterization, biological activity evaluation (against MES model), in-silico biological activity spectrum (PASS analysis), toxicological and predicted oral rat LD50 studies of novel sulphonamide derivatives[J]. Front. Biol., 2018, 13(6): 425-451.
 URL:  
http://journal.hep.com.cn/fib/EN/10.1007/s11515-018-1512-4
http://journal.hep.com.cn/fib/EN/Y2018/V13/I6/425
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Ajeet
Arvind Kumar
Arun K. Mishra
Basic identified pharmacophore
Tab.1  Pharmacophoric pattern of well-known anticonvulsants
Fig.12  Scheme 1. Synthetic scheme of substituted 4-amino-benzenesulfonamide from substituted acids (1a-1c)
Fig.13  Scheme 2. Synthetic scheme of substituted 4-amino-benzenesulfonamide from (Chloro-substituted)-substituted benzene (2a-2q)
Fig.14  Common reaction mechanism of schemes employed.
Compound Structure
1a
1b
1c
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
Tab.2  Designed molecules
Comp. Molec. mass AlogP nHBD nHBA MR Lipinski failure
1a 276.0569 0.1463 2 5 77.93 0
1b 302.0725 0.5074 2 5 88.1735 0
1c 282.0133 -0.5031 2 5 75.1944 0
2a 277.0885 -0.8244 2 5 82.0505 0
2b 292.0882 -0.1263 2 5 85.1442 0
2c 292.0882 -0.1263 2 5 85.1442 0
2d 292.0882 -0.1263 2 5 85.1442 0
2e 277.0885 -0.8244 2 5 82.0505 0
2f 277.0885 -0.8244 2 5 82.0505 0
2g 304.0882 -0.0772 2 5 88.051 0
2h 291.1041 -0.5616 2 5 86.2149 0
2i 291.1041 -0.5616 2 5 86.2149 0
2j 318.1038 0.1856 2 5 92.2154 0
2k 318.1038 0.1856 2 5 92.2154 0
2l 319.1354 0.00254 3 5 95.1185 0
2m 319.1354 0.00254 3 5 95.1185 0
2n 319.1354 0.00254 3 5 95.1185 0
2o 334.1351 0.419515 2 5 98.2122 0
2p 334.1351 0.419515 2 5 98.2122 0
2q 334.1351 0.419515 2 5 98.2122 0
Tab.3  Descriptors of Lipinski Rule of Five
Ligand Affinity
kcal/mol
H-
bond
H- binding ligand H- binding receptor
Elem At. ID Type Residue Elem At.ID Type
1a -7.7 6 O 19 Acceptor Thr199 N 196 Donor
O 19 Acceptor Thr199 O 201 Both
N 20 Donor Thr199 O 201 Both
N 20 Donor His96 N 94 Acceptor
N 20 Donor His94 N 82 Acceptor
O 18 Acceptor His119 N 113 Donor
1b -7.7 7 O 21 Acceptor Thr199 N 196 Donor
O 21 Acceptor Thr199 O 201 Both
N 22 Donor Thr199 O 201 Both
N 22 Donor His96 N 94 Acceptor
N 22 Donor His94 N 82 Acceptor
O 20 Acceptor His119 N 113 Donor
O 9 Acceptor Gln92 N 69 Donor
1c -7.2 7 O 18 Acceptor Thr199 N 196 Donor
O 18 Acceptor Thr199 O 201 Both
N 19 Donor Thr199 O 201 Both
N 19 Donor His96 N 94 Acceptor
N 19 Donor His94 N 82 Acceptor
O 17 Acceptor His119 N 113 Donor
O 9 Acceptor Gln92 N 69 Donor
2a -7.3 6 O 21 Acceptor Thr199 N 196 Donor
O 21 Acceptor Thr199 O 201 Both
N 22 Donor Thr199 O 201 Both
N 22 Donor His96 N 94 Acceptor
N 22 Donor His94 N 82 Acceptor
O 20 Acceptor His119 N 113 Donor
2b -7.3 6 O 20 Acceptor Thr199 N 196 Donor
O 20 Acceptor Thr199 O 201 Both
N 21 Donor Thr199 O 201 Both
N 21 Donor His96 N 94 Acceptor
N 21 Donor His94 N 82 Acceptor
O 19 Acceptor His119 N 113 Donor
2c -7.3 6 O 20 Acceptor Thr199 N 196 Donor
O 20 Acceptor Thr199 O 201 Both
N 21 Donor Thr199 O 201 Both
N 21 Donor His96 N 94 Acceptor
N 21 Donor His94 N 82 Acceptor
O 19 Acceptor His119 N 113 Donor
2d -7.3 6 O 20 Acceptor Thr199 N 196 Donor
O 20 Acceptor Thr199 O 201 Both
N 21 Donor Thr199 O 201 Both
N 21 Donor His96 N 94 Acceptor
N 21 Donor His94 N 82 Acceptor
O 19 Acceptor His119 N 113 Donor
2e -7.3 6 O 21 Acceptor Thr199 N 196 Donor
O 21 Acceptor Thr199 O 201 Both
N 22 Donor Thr199 O 201 Both
N 22 Donor His96 N 94 Acceptor
N 22 Donor His94 N 82 Acceptor
O 20 Acceptor His119 N 113 Donor
2f -7.2 6 O 21 Acceptor Thr199 N 196 Donor
O 21 Acceptor Thr199 O 201 Both
N 22 Donor Thr199 O 201 Both
N 22 Donor His96 N 94 Acceptor
N 22 Donor His94 N 82 Acceptor
O 20 Acceptor His119 N 113 Donor
2g -7.4 6 O 21 Acceptor Thr199 N 196 Donor
O 21 Acceptor Thr199 O 201 Both
N 22 Donor Thr199 O 201 Both
N 22 Donor His96 N 94 Acceptor
N 22 Donor His94 N 82 Acceptor
O 20 Acceptor His119 N 113 Donor
2h -7.2 6 O 10 Acceptor Thr199 N 196 Donor
O 10 Acceptor Thr199 O 201 Both
N 11 Donor Thr199 O 201 Both
N 11 Donor His96 N 94 Acceptor
N 11 Donor His94 N 82 Acceptor
O 9 Acceptor His119 N 113 Donor
2i -7.2 6 O 10 Acceptor Thr199 N 196 Donor
O 10 Acceptor Thr199 O 201 Both
N 11 Donor Thr199 O 201 Both
N 11 Donor His96 N 94 Acceptor
N 11 Donor His94 N 82 Acceptor
O 9 Acceptor His119 N 113 Donor
2j -7.4 6 O 10 Acceptor Thr199 N 196 Donor
O 10 Acceptor Thr199 O 201 Both
N 11 Donor Thr199 O 201 Both
N 11 Donor His96 N 94 Acceptor
N 11 Donor His94 N 82 Acceptor
O 9 Acceptor His119 N 113 Donor
2k -7.4 6 O 10 Acceptor Thr199 N 196 Donor
O 10 Acceptor Thr199 O 201 Both
N 11 Donor Thr199 O 201 Both
N 11 Donor His96 N 94 Acceptor
N 11 Donor His94 N 82 Acceptor
O 9 Acceptor His119 N 113 Donor
2l -7.0 6 O 11 Acceptor Thr199 N 196 Donor
O 11 Acceptor Thr199 O 201 Both
N 12 Donor Thr199 O 201 Both
N 12 Donor His96 N 94 Acceptor
N 12 Donor His94 N 82 Acceptor
O 10 Acceptor His119 N 113 Donor
2m -6.5 6 O 11 Acceptor Thr199 N 196 Donor
O 11 Acceptor Thr199 O 201 Both
N 12 Donor Thr199 O 201 Both
N 12 Donor His96 N 94 Acceptor
N 12 Donor His94 N 82 Acceptor
O 10 Acceptor His119 N 113 Donor
2n -6.6 7 O 11 Acceptor Thr199 N 196 Donor
O 11 Acceptor Thr199 O 201 Both
N 12 Donor Thr199 O 201 Both
N 12 Donor His96 N 94 Acceptor
N 12 Donor His94 N 82 Acceptor
O 10 Acceptor His119 N 113 Donor
N 25 Donor Pro201 O 220 Acceptor
2o -7.0 6 O 10 Acceptor Thr199 N 196 Donor
O 10 Acceptor Thr199 O 201 Both
N 11 Donor Thr199 O 201 Both
N 11 Donor His96 N 94 Acceptor
N 11 Donor His94 N 82 Acceptor
O 9 Acceptor His119 N 113 Donor
2p -6.8 6 O 10 Acceptor Thr199 N 196 Donor
O 10 Acceptor Thr199 O 201 Both
N 11 Donor Thr199 O 201 Both
N 11 Donor His96 N 94 Acceptor
N 11 Donor His94 N 82 Acceptor
O 9 Acceptor His119 N 113 Donor
2q -6.7 5 O 10 Acceptor Thr199 N 196 Donor
O 10 Acceptor Thr199 O 201 Both
N 11 Donor Thr199 O 201 Both
N 11 Donor His96 N 94 Acceptor
N 11 Donor His94 N 82 Acceptor
Zonisamide -6.3 6 N 14 Donor Thr199 O 201 Both
N 14 Donor His96 N 94 Acceptor
N 14 Donor His92 N 82 Acceptor
O 13 Acceptor Thr199 O 201 Both
O 18 Acceptor Thr199 N 196 Donor
O 12 Acceptor His119 N 113 Donor
Acetazolmide -6.4 5 N 15 Donor His94 N 82 Acceptor
N 15 Donor His96 N 94 Acceptor
N 15 Donor Thr199 O 201 Both
O 14 Acceptor Thr199 O 201 Both
O 14 Acceptor Thr199 N 196 Donor
Tab.4  Docking results of all the compounds with receptor 1AZM
Fig.35  Docked images of designed molecules 1a, 1b, 1c, 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2l, 2m, 2n, 2o, 2p and 2q with 1AZM
Comp. Molecular formula (MW) Yield (%) MP (°C) Elemental analysis (%): Found (Calculated) % purity Rf
C H N S
1a C13H12N2O3S (276.056) 68.75 205-208 56.42 (56.50) 3.260 (4.37) 10.13 (10.14) 11.16 (11.60) 98.00 0.42
1b C15H14N2O3S (302.072) 71.92 220-222 59.44 (59.58) 1.922 (4.66) 9.224 (9.26) 10.63 (10.60) 96.55 0.80
1c C11H10N2O3S2 (282.013) 56.73 210-212 39.89 (46.77) 0.969 (3.56) 8.540 (9.92) 19.16 (22.73) 82.59 0.63
2a C13H15N3O2S (277.088) 88.42 215-217 56.01 (56.30) 4.98 (5.45) 14.05 (15.15) 11.14 (11.56) 97.42 0.39
2b C14H16N2O3S
(292.088)
68.22 209-211 56.81 (57.52) 4.99 (5.52) 9.42 (9.58) 10.00 (10.97) 97.16 0.41
2c C14H16N2O3S (292.088) 67.80 184-186 57.05 (57.52) 5.10 (5.52) 9.50 (9.58) 10.88 (10.97) 98.72 0.43
2d C14H16N2O3S (292.088) 62.00 180-182 57.10 (57.52) 5.04 (5.52) 9.48 (9.58) 10.02 (10.97) 97.88 0.49
2e C13H15N3O2S (277.088) 85.88 190-192 56.09 (56.30) 4.93 (5.45) 14.87 (15.15) 11.01 (11.56) 98.23 0.48
2f C13H15N3O2S (277.088) 80.02 185-187 56.02 (56.30) 4.92 (5.45) 15.01 (15.15) 11.32 (11.56) 98.65 0.52
2g C15H16N2O3S (304.088) 82.44 194-197 58.09 (59.19) 5.10 (5.30) 9.17 (9.20) 9.28 (10.54) 96.92 0.45
2h C14H17N3O2S (291.104) 88.33 198-200 56.87 (57.71) 4.98 (5.88) 14.02 (14.42) 10.31 (11.00) 96.82 0.51
2i C14H17N3O2S (291.104) 86.53 200-202 56.76 (57.71) 5.06 (5.88) 13.82 (14.42) 10.32 (11.00) 96.57 0.47
2j C16H18N2O3S (318.103) 61.21 197-200 59.62 (60.36) 4.94 (5.70) 8.13 (8.80) 9.89 (10.07) 97.23 0.58
2k C16H18N2O3S (318.103) 60.54 188-190 60.05 (60.36) 4.38 (5.70) 8.13 (8.80) 9.22 (10.07) 96.29 0.38
2l C16H21N3O2S (319.135) 89.12 204-206 59.01 (60.16) 4.32 (6.63) 11.32 (13.16) 8.98 (10.04) 92.93 0.53
2m C16H21N3O2S (319.135) 86.78 203-205 59.41 (60.16) 5.41 (6.63) 12.33 (13.16) 9.07 (10.04) 95.81 0.33
2n C16H21N3O2S (319.135) 81.89 187-189 58.97 (60.16) 6.41 (6.63) 12.84 (13.16) 9.65 (10.04) 97.64 0.50
2o C17H22N2O3S (334.135) 61.22 206-208 60.22 (61.05) 5.44 (6.63) 7.96 (8.38) 8.95 (9.59) 96.40 0.36
2p C17H22N2O3S (334.135) 60.22 183-185 60.86 (61.05) 5.78 (6.63) 8.02 (8.38) 9.01 (9.59) 97.68 0.40
2q C17H22N2O3S (334.135) 59.35 196-198 57.88 (61.05) 4.53 (6.63) 7.31 (8.38) 8.98 (9.59) 91.88 0.61
Tab.5  Physical and elemental data of all the synthesized compounds
Fig.36  
Fig.37  
Fig.38  
Fig.39  
Fig.40  
Fig.41  
Fig.42  
Fig.43  
Fig.44  
Fig.45  
Fig.46  
Fig.47  
Fig.48  
Fig.49  
Fig.50  
Fig.51  
Fig.52  
Fig.53  
Fig.54  
Fig.55  
Oral administration to rat a
Comp. Dose (mg/kg) 30 minc 2 hc Neurotox.b
30 min 4 h
1a 100 4/6 6/6 0/4 0/4
1b 100 5/6 6/6 0/4 0/4
1c 100 3/6 5/6 0/4 0/4
2a 100 3/6 4/6 0/4 0/4
2b 100 3/6 4/6 0/4 0/4
2c 100 2/6 4/6 0/4 0/4
2d 100 3/6 4/6 0/4 0/4
2e 100 3/6 5/6 0/4 0/4
2f 100 4/6 4/6 0/4 0/4
2g 100 6/6 6/6 0/4 0/4
2h 100 4/6 5/6 0/4 0/4
2i 100 5/6 5/6 0/4 0/4
2j 100 4/6 5/6 0/4 0/4
2k 100 5/6 6/6 0/4 0/4
2l 100 2/6 3/6 0/4 0/4
2m 100 2/6 4/6 0/4 0/4
2n 100 2/6 3/6 0/4 0/4
2o 100 4/6 6/6 0/4 0/4
2p 100 2/6 3/6 0/4 0/4
2q 100 2/6 3/6 0/4 0/4
Acetazola-mide 100 6/6 6/6 0/4 0/4
Tab.6  Anticonvulsant (MES) activity and neurotoxicity of synthesized compounds
Compound Time taken (s)+
Flexion Extensor Clonus Stupor
1a 1.68±0.09*** 2.78±0.07*** 1.78±0.07 *** 7.1±0.24***
1b 2.18±0.07 *** 3.28±0.07 *** 2.38±0.06*** 7.1±0.20***
1c 3.99±0.06 ** 4.31±0.08 *** 10.50±0.18 *** 10.88±0.11 ***
2a 4.3±0.08 ns 4.9±0.16 *** 11.20±0.18 *** 11.18±0.21***
2b 3.36±0.06 *** 4.04±0.13*** 7.65±0.12 *** 9.65±0.22 ***
2c 4.31±0.07ns 4.94±0.20 *** 10.71±0.15 *** 10.64±0.12 ***
2d 4.16±0.10 ns 5.1±0.12 *** 11.21±0.16*** 11.26±0.14 ***
2e 4.10±0.09 * 4.76±0.18 *** 10.98±0.20 *** 11.17±0.20***
2f 4.48±0.11 ns 4.79±0.23 *** 11.1±0.25 *** 11.6±0.18***
2g 1.74±0.12 *** 1.88±0.07*** 1.99±0.13*** 6.64±0.14***
2h 4.435±0.14 ns 4.8±0.21*** 10.77±0.23*** 11.11±0.22***
2i 4.32±0.14 ns 4.8±0.17 *** 10.83±0.22*** 11.5±0.27 ***
2j 4.18±0.11 ns 4.78±0.26 *** 10.85±0.26 *** 11.40±0.22***
2k 1.76±0.17 *** 3.07±0.16 *** 1.88±0.14 *** 6.70±0.24 ***
2l 7.91±0.18*** 8.14±0.22*** 12.73±0.62*** 96.96±0.28 ***
2m 8.07±0.17 *** 7.44±0.22 *** 13.72±0.17 *** 97.79±0.33 ***
2n 7.88±0.25 *** 7.97±0.25*** 14.06±0.18*** 96.98±0.30***
2o 1.93±0.16 *** 2.8±0.13 *** 2.2±0.29*** 7.05±0.23***
2p 7.62±0.22 *** 7.89±0.17 *** 13.69±0.26*** 98.62±0.12***
2q 8.23±0.27*** 8.35±0.19*** 13.79±0.22*** 98.16±0.12***
Acetazolamide 2.01±0.13*** 0±0.26 *** 2.8±0.31*** 2.6±0.21***
Control: HPMC 5% w/v 4.5±0.30 18.7±0.97 15.06±0.97 13.1±0.89
Tab.7  Anticonvulsant effect on all phases of MES model
Comp. CA I inhibitor CA II inhibitor CA IV inhibitor CA IX inhibitor CA V inhibitor CA VII inhibitor CA XII inhibitor CA XIV inhibitor
1a 0.180 0.186 0.104 0.180 0.440 0.220 0.140 0.101
1b 0.050 0.128 0.032 0.108 0.262 0.188 0.090 0.105
1c 0.040 0.252 0.093 0.111 0.118 0.172 0.086 0.073
2a 0.161 0.193 0.102 0.195 0.424 0.206 0.135 0.067
2b 0.034 0.074 0.020 0.084 0.107 0.150 0.070 0.068
2c 0.025 0.054 0.015 0.060 0.090 0.136 0.060 0.058
2d 0.021 0.041 0.013 0.063 0.080 0.140 0.063 0.063
2e 0.117 0.157 0.072 0.162 0.343 0.186 0.108 0.058
2f 0.068 0.085 0.042 0.152 0.230 0.181 0.100 0.063
2g 0.027 0.051 0.014 0.056 0.104 0.135 0.060 0.051
2h 0.179 0.291 0.139 0.197 0.399 0.205 0.142 0.064
2i 0.145 0.249 0.112 0.166 0.374 0.184 0.113 0.056
2j 0.034 0.104 0.020 0.090 0.096 0.158 0.081 0.065
2k 0.025 0.083 0.016 0.062 0.087 0.141 0.068 0.062
2l 0.225 0.284 0.163 0.169 0.411 0.198 0.151 0.058
2m 0.201 0.242 0.127 0.142 0.384 0.179 0.123 0.050
2n 0.149 0.167 0.088 0.119 0.255 0.168 0.107 0.050
2o 0.073 0.111 0.036 0.080 0.096 0.157 0.091 0.066
2p 0.043 0.086 0.022 0.059 0.038 0.081 0.142 0.076
2q 0.033 0.073 0.019 0.054 0.086 0.142 0.076 0.064
Tab.8  Biological activity Spectrum against Carbonic anhydrase (Probability to be active)
Comp. Mutagenicity Skin irritancy Method employed
Probability Status Probability Status
1a 0.020 Non-Mutagen 0.043 Non-irritant Consensus
1b 0.020 Non-Mutagen 0.012 Non-irritant Consensus
1c 0.300 Non-Mutagen 0.025 Non-irritant Consensus
2a 0.398 Non-Mutagen 0.058 Non-irritant TOPKAT®
2b 0.366 Non-Mutagen 0.014 Non-irritant TOPKAT®
2c 0.349 Non-Mutagen 0.187 Non-irritant TOPKAT®
2d 0.418 Non-Mutagen 0.524 Non-irritant TOPKAT®
2e 0.450 Non-Mutagen 0.011 Non-irritant TOPKAT®
2f 0.468 Non-Mutagen 0.570 Non-irritant TOPKAT®
2g 0.330 Non-Mutagen 0.162 Non-irritant TOPKAT®
2h 0.575 Non-Mutagen 0.662 Non-irritant TOPKAT®
2i 0.551 Non-Mutagen 0.597 Non-irritant TOPKAT®
2j 0.314 Non-Mutagen 0.947 Non-irritant TOPKAT®
2k 0.354 Non-Mutagen 0.910 Non-irritant TOPKAT®
2l 0.537 Non-Mutagen 0.481 Non-irritant TOPKAT®
2m 0.459 Non-Mutagen 0.360 Non-irritant TOPKAT®
2n 0.494 Non-Mutagen 0.314 Non-irritant TOPKAT®
2o 0.325 Non-Mutagen 0.908 Non-irritant TOPKAT®
2p 0.255 Non-Mutagen 0.728 Non-irritant TOPKAT®
2q 0.170 Non-Mutagen 0.543 Non-irritant Consensus
Tab.9  Probability and current status to be mutagenic and skin irritant of designed screened compound
Compound Oral rat LD50 (g/kg)
1a 5.27
1b 4.33
1c 0.810
2a 2.87
2b 4.15
2c 4.59
2d 4.54
2e 3.27
2f 5.13
2g 2.66
2h 3.12
2i 3.25
2j 2.82
2k 2.66
2l 2.71
2m 2.99
2n 3.21
2o 1.71
2p 4.27
2q 2.92
Tab.10  Predicted oral rat LD50
Fig.56  Carbonic anhydrase inhibitors.
1 Barry Wood W (1942). Studies on the antibacterial action of the sulfonamide drugs. J Exp Med, 75(4): 369–381
https://doi.org/10.1084/jem.75.4.369 pmid: 19871190
2 Bialk H M, Simpson A J, Pedersen J A (2005). Cross-coupling of sulfonamide antimicrobial agents with model humic constituents. Environ Sci Technol, 39(12): 4463–4473
https://doi.org/10.1021/es0500916 pmid: 16047782
3 Capasso C, Supuran C T (2015). An overview of the alpha-, beta- and gamma-carbonic anhydrases from Bacteria: can bacterial carbonic anhydrases shed new light on evolution of bacteria? J Enzyme Inhib Med Chem, 30(2): 325–332
https://doi.org/10.3109/14756366.2014.910202 pmid: 24766661
4 De Simone G, Scozzafava A, Supuran C T (2009). Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des, 74(3): 317–321
https://doi.org/10.1111/j.1747-0285.2009.00857.x pmid: 19703035
5 Filimonov D A, Poroikov V V, Karaicheva E I, Kazarian R K, Budunova A P, Mikhailovskii E M, Rudnitskikh A V, Goncharenko L V, Burov Yu V (1995). Computer-Aided Prediction of Biological Activity Spectra of Chemical Substances on the Basis of Their Structural Formulae: Computerized System PASS. Experimental and Clinical Pharmacology(Rus), 58(2): 56–62
6 Hen N, Bialer M, Wlodarczyk B, Finnell R H, Yagen B (2010). Syntheses and evaluation of anticonvulsant profile and teratogenicity of novel amide derivatives of branched aliphatic carboxylic acids with 4-aminobenzensulfonamide. J Med Chem, 53(10): 4177–4186
https://doi.org/10.1021/jm100170w pmid: 20420384
7 Leeson P (2012). Drug discovery: Chemical beauty contest. Nature, 481(7382): 455–456
https://doi.org/10.1038/481455a pmid: 22281594
8 Malawska B, Scatturin A (2003). Application of pharmacophore models for the design and synthesis of new anticonvulsant drugs. Mini Rev Med Chem, 3(4): 341–348
https://doi.org/10.2174/1389557033488088 pmid: 12678827
9 Masereel B, Rolin S, Abbate F, Scozzafava A, Supuran C T (2002). Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. J Med Chem, 45(2): 312–320
https://doi.org/10.1021/jm0109199 pmid: 11784136
10 Perrin H L, Bliss E A (1937). Para-aminobenzenesulfonamide and its derivatives experimental and clinical observations on their use in the treatment of betahemolytic streptococcic infection: a preliminary report. J. Am. Med. Soc., 108(1): 32–37
11 Price T, Sammons G, Zachry D (1952). Antitubercular Studies. V. 4-Aminobenzamides and 4-Aminobenzenesulfonamides. J Am Chem Soc, 74(23): 5961–5963
https://doi.org/10.1021/ja01143a042
12 Reynolds C H, Merz K M, Ringe D( 2010 ) . Drug Design: Structure- And Ligand-Based Approaches, Cambridge University Press, Cambridge UK
13 Reynolds E H (2002). Epilepsy in the world: Launch of the second phase of the ILAE/IBE/WHO global campaign against epilepsy. Epilepsia, 43(supp. 6): 1–3
https://doi.org/10.1046/j.1528-1157.43.s.6.1.x pmid: 12190964
14 Satischandra P, Gururaj G, Mohammed Q D, Senanayake N, Silpakit O, Dekker P A( 2005). Epilepsy: A manual for physicians. World Health Organization, New Delhi.1–15
15 Supuran C T (2008). Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov, 7(2): 168–181
https://doi.org/10.1038/nrd2467 pmid: 18167490
16 Thiry A, Dogné J M, Supuran C T, Masereel B (2007). Carbonic anhydrase inhibitors as anticonvulsant agents. Curr Top Med Chem, 7(9): 855–864
https://doi.org/10.2174/156802607780636726 pmid: 17504130
17 Thiry A, Dogné J M, Supuran C T, Masereel B (2008). Anticonvulsant sulfonamides/sulfamates/sulfamides with carbonic anhydrase inhibitory activity: drug design and mechanism of action. Curr Pharm Des, 14(7): 661–671
https://doi.org/10.2174/138161208783877956 pmid: 18336312
18 Tripathi L, Kumar P, Singh R, Stables J P (2012). Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-(4-(substituted) benzylidene)-hydrazinecarbothio amides. Eur J Med Chem, 47(1): 153–166
https://doi.org/10.1016/j.ejmech.2011.10.038 pmid: 22082834
19 Trott O, Olson A J (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem, 31(2): 455–461
pmid: 19499576
20 Vannada J, Bennett E M, Wilson D J, Boshoff H I, Barry C E 3rd, Aldrich C C (2006). Design, synthesis, and biological evaluation of beta-ketosulfonamide adenylation inhibitors as potential antitubercular agents. Org Lett, 8(21): 4707–4710
https://doi.org/10.1021/ol0617289 pmid: 17020283
21 Venkatapathy R, Moudgal C J, Bruce R M (2004). Assessment of the oral rat chronic lowest observed adverse effect level model in TOPKAT, a QSAR software package for toxicity prediction. J Chem Inf Comput Sci, 44(5): 1623–1629
https://doi.org/10.1021/ci049903s pmid: 15446819
22 Zimmerman S, Innocenti A, Casini A, Ferry J G, Scozzafava A, Supuran C T (2004). Carbonic anhydrase inhibitors. Inhibition of the prokariotic beta and gamma-class enzymes from Archaea with sulfonamides. Bioorg Med Chem Lett, 14(24): 6001–6006
https://doi.org/10.1016/j.bmcl.2004.09.085 pmid: 15546717
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