CODEN (USA): IJCRGG, ISSN: 0974-4290, ISSN(Online):2455-9555 Vol.10 No.7, pp 401-408, 2017
Abstract : As a part of systematic investigations a series of novel N-{(1,3-benzo[d]thiazol-2yl)carbamothioyl}-2/4-substituted benzamides3a-gwere synthesized by the reaction of 2aminobenzothiazole 1with benzoyl isothiocyanates 2a-g.The structure elucidation of these compounds was completed by means of chemical tests, elemental (C, H, N and S) and spectral (IR, 1H NMR and mass) analysis. All of them were screened for their antibacterial activity against Gram positive and Gram negative bacteria showing promising results, and have shown moderate to potent antibacterial activity comparable to standard drugs. Physiochemical parameters, toxicity profiles and drug likeness properties were studied using bioinformaticals tools like molinspiration.
Benzamides are considered as advantaged scaffold which played a noticeable role for increasing the biological activities and so far, they have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry.They have been reported to play a crucial role in drug development1. Benzamides derivatives, e.g. metoclopramide and cisapride are used clinically for the treatment of different medical conditions2. Benzamides are important structural unit present in many compounds having potential biological activities, For example, molecules, like proteins which play an essential role in almost all biological processes such as enzymatic catalysis (nearly all known enzymes are proteins), transport/storage (haemoglobin), immune protection (antibodies) and mechanical support (collagen). Benzamides are known for
345 6
their anti-inflammatory and immunomodulatory, anti-tumoral, antipsychotic, antituberculosis, antifungal,
789 1011 12
antiviral, analgesic, anticonvulsant, antiinflammatory, antibacterial, antimalarial, anthelminticand anticancer13etc. activities.
Benzothiazole is one of the most important heterocycle that has received overwhelming response owing to its diversified molecular design and remarkable optical, liquid and electronic properties14. N-Substituted benzothiazoles are highly reactive and hence extensively utilized as reactant or reaction intermediates. Presece of-NH2 and endocylic N functions are suitably situated to enable reaction with common electrophillic agents to form a variety of fused heterocyclic compounds15.Hence synthesis of new compounds containing benzothiazole nucleus involved in research are of considerable interest.
Keeping all these facts in mind, it was thought to study comprehensive account of the synthetic utility of 2-aminobenzothiazoles in building novel benzamides and aimed to evaluate them for biological activities.
Before actual synthesis, our interest is in the study of theoretical molecular properties. Thus molinspiration software program 16was used to predict different theoretical properties such as toxicity risk, solubility, drug likeness. Recently, many researchers have use these tools successfully and presented the
17-20
correlations with the experimentally found pharmacological activities.
The structural elucidation of newly synthesized compounds was done using spectroscopic tools such as IR, 1H NMR, 13C NMR, Mass and elemental analysis technique. The end products were evaluated for their antimicrobial activity using well diffusion method.
All reactions were performed in oven-dried glassware’s with magnetic stirring. All the chemicals and solvents are obtained from E-Merck, India (AR grade) and were used without further purification. Melting points of compounds were taken in an open capillary tubes by Toshniwal melting point apparatus in Celsius scale and uncorrected. The purity of the compound was verified by performing thin layer chromatography (TLC) on silica gel G (Merck) coated glass plates and spots were visualized by exposure to iodine vapors using Toluene : ethyl acetate (1:1) as a solvent system. IR spectra were recorded using KBr pellets on FTIR spectrophotometer (Perkin Elmer -Spectrum RX-IFTIR). 1H-NMR spectra were recorded on sophisticated multinuclear FT NMR Spectrometer model Advance-II (Bruker) (CIL, Chandigarh, India); 1H frequency is 400 MHz Chemical shift (δ) are expressed in ppm relative to tetra methyl silane (TMS) as an internal standard. Mass spectra (FAB-MS) were recorded on Waters Micromass Q-T of Microspectrophotometer (SAIF, Chandigarh, India) and elemental analysis were carried out using Elementar Vario EL III CHN analyzer (STIC India, Cochin).
The mixture of aniline (0.25 mole), HCl (0.25 mole ) and ammonium thiocyanate ( 0.12 mole ) 30g in 60 ml water on refluxing for 3 hours gave phenyl thiourea, which on vigorous stirring with bromine for 10 hours at room temperature produced corresponding hydrobromide which was converted into 2aminobenzothiazole 1 upon basification. The yields of the respective 2-aminobenzothiazoles were found to be excellent.
Substituted benzoyl chloride (0.1 mole) was added dropwise on to a solution of ammonium thiocyanate (0.1 mole) in dry benzene (25ml) with vigorous stirring. The mixture was boiled for two hours. Cooled and filtered. Substituted benzoyl isothiocyanates 2a-g were obtained in the form of liquid.
2-aminobenzothiazole (0.01mole) 1 and substituted benzoyl isothiocyanates (0.01mole) 2a-g were refluxed in a mixture of dry benzene (25ml) and 2-propanol (5ml) for 3 hours. The solid material obtained was filtered, dried and recrystallized from benzene. The spectral data of 3a-g are given below.
m.p.: 1890C; IR (KBr, νmax, cm -1): 1058.13 (C=S, stretching), 1490.11 (Ar C=C, stretching), 1612.11 (C=N, stretching), 1677.17 (C=O, stretching), 3086.18 (Ar C-H, stretching), 3343.17, 3401.16 (NH, stretching); 1H NMR (DMSO, δ, ppm), 7.52-8.07 (m, 9H, Ar-H), 8.18 (s, 1H, NHC=O, D2O exchangeble), 12.28 (bs, 1H, NHC=S, D2O exchangeable), 13C-NMR spectrum displayed signals at δ 187.58 (s, C-1, C=S), 167.16 (s, C-1, C-NH), 165.18 (s, C-1, C=O), and other singlet’s at 113.75, 121.36, 126.94, 128.18, 129.28, 129.71, 131.09 for –CH carbon and 135.09, 136.33, 147.23 for for –C; Mass spectra, (EI) m/z: 313.03 (M+ peak).
m.p.: 2540C; IR (KBr, νmax, cm -1): 801.12 (C-Cl, stretching), 1052.13 (C=S, stretching), 1544.15 (Ar C=C, stretching), 1642.71 (C=N, stretching), 1652.31 (C=O, stretching), 3106.24 (Ar C-H, stretching), 3368.34, 3143.54 (NH, stretching); 1H NMR (DMSO, δ, ppm): 7.58-8.28 (m, 8H, Ar-H), 8.84 (s, 1H, NHC=O, D2O exchangeble), 13.05 (bs, 1H, NHC=S, D2O exchangeable); 13C-NMR spectrum displayed signals at δ 177.52 (s, C-1, C=S), 172.16 (s, C-1, -C-NH), 164.13 (s, C-1, C=O), and other singlet’s at 115.6, 122.3, 124.6, 125.5, 128.8, 130.2, 131.3 for –CH and 131.8, 138.7, 154.2for –C; Mass spectra, (EI) m/z: 347 (M+ peak).
m.p.: 1990C; IR (KBr, νmax, cm -1): 1091.13 (C=S, stretching), 1461 (CH3, bend), 1591.18 (Ar C=C, stretching), 1598.73 (C=N, stretching), 1677.34 (C=O, stretching), 2923 (C–H, stretching), 3082.19 (Ar C-H, stretching), 3288.31, 3174.49 ( NH, stretching); 1H NMR (DMSO, δ, ppm): 7.42-8.18 (m, 8H, Ar-H), 9.73 (s, 1H, NHC=O, D2O exchangeble), 12.82 (bs, 1H, NHC=S, D2O exchangeable), 2.37 (s, 3H, CH3); Mass spectra, 13C-NMR spectrum displayed signals at δ 177.52 (s, C-1, C=S), 172.16 (s, C-1, -C-NH), 164.13 (s, C-1, C=O), and other singlet’s at 21.6, 117.4, 120.5, 125.4, 126.8, 129.7, 131.3, 132.4 for –CH and 132.6, 139.4, 149.3 for –C; Mass spectra,; (EI) m/z: 327(M+ peak).
m.p.: 1720C; IR (KBr, νmax, cm -1): 1123.83 (C=S, stretching), 1583.18 (Ar C=C, stretching), 1568.53 (C=N, stretching), 1681.14 (C=O, stretching), 2768 (O-CH3, stretching), 2936.74 (C–H Aliph, stretching), 3071.13 (Ar C-H, stretching), 3381.39, 3167.37 (NH, stretching); 1H NMR (DMSO, δ, ppm): 7.22-8.12 (m, 8H, Ar-H),
8.20 (s, 1H, NHC=O, D2O exchangeble), 12.59 (bs, 1H, NHC=S, D2O exchangeable), 3.82 (s, 1H, OCH3); 13CNMR spectrum displayed signals at 178.32 (s, C-1, C=S), 171.18 (s, C-1, -C-NH), 163.14 (s, C-1, C=O), 55.16 (s, C-1, -OCH3), and other singlet’s at 114.6, 119.2, 122.7, 124.2, 124.9, 125.6 for –CH and also singlet at 126.8, 130.8, 155.2, 163.2 for –C;Mass spectra, (EI) m/z: 343 (M+ peak).
m.p.: 2680C; IR (KBr, νmax, cm -1): 1113.16 (C=S, stretching), 1326 (C-NO2,stretching), 1498.03 (Ar C=C, stretching), 1623.91 (C=N, stretching), 1661.80 (C=O, stretching), 3086.47 (Ar C-H, stretching), 3396.41, 3184.76 (NH, stretching); 1H NMR (DMSO, δ, ppm): 7.25-8.26 (m, 8H, Ar-H), 9.86 (s, 1H, NHC=O, D2O exchangeble), 13.02 (bs, 1H, NHC=S, D2O exchangeable); 13C-NMR spectrum displayed signals at 181.34 (s, C-1, C=S), 176.15 (s, C-1, -C-NH), 163.14 (s, C-1, C=O), singlet for –CH at 116.9, 122.5, 124.1, 124.8, 125.6, 129.6, and also singlet at 130.5, 140.3, 154.2, for –C; Mass spectra (EI) m/z: 358.02 (M+ peak).
m.p.: 2530C; IR (KBr, νmax, cm -1): 768.12 (C-Cl, stretching), 1098.26 (C=S, stretching), 1581.46 (Ar C=C, stretching), 1597.23 (C=N, stretching), 1678.31 (C=O, stretching), 3036.74 (Ar C-H stretching), 3407.94, 3118.65 (NH, stretching); 1H NMR (DMSO, δ, ppm): 7.47-7.95 (m, 8H, Ar-H), 8.17 (s, 1H, NHC=O, D2O exchangeble), 12.98 (bs, 1H, NHC=S, D2O exchangeable); 13C-NMR spectrum displayed signals at 181.34 (s, C-1, C=S), 176.15 (s, C-1, -C-NH), 163.14 (s, C-1, C=O), singlet for –CH at 117.5, 122.8, 124.6, 125.8, 127.9, 128.1, 130.5, 131.6, 133.9 and also singlet at 130.9, 132.5, 134.1, 153.7 for –C; Mass spectra (EI) m/z: 347(M+ peak).
m.p.: 2010C; IR (KBr, νmax, cm -1): 1068.9 (C=S, stretching), 1470 (CH3, bend), 1587.13 (Ar C=C, stretching), 1601.62 (C=N, stretching), 1676.42 (C=O, stretching), 2928 (C–H, stretching), 3084.36 (Ar C-H, stretching), 3289.11, 3179.78 ( NH, stretching); 1H NMR (DMSO, δ, ppm): 7.43-8.21 (m, 8H, Ar-H), 9.76 (s, 1H, NHC=O, D2O exchangeble), 12.91 (bs, 1H, NHC=S, D2O exchangeable), 2.46 (s, 3H, CH3); 13C-NMR spectrum displayed signals at δ 13C-NMR spectrum displayed signals at δ 182.52 (s, C-1, C=S), 175.16 (s, C-1, -C-NH),
166.15 (s, C-1, C=O), 19.1 (s, C-1, -CH3), singlet for –CH at 116.7, 123.8, 124.5, 125.3, 128.7, 131.5, 132.6,
134.5 and also singlet at 126.2, 130.8, 137.5, 153.6 for –C; Mass spectra, (EI) m/z: 327(M+ peak).
The newly synthesized N-{[(1,3-benzo[d]thiazol-2-ylcarbamothioyl)-2/4-substituted benzamides3a-g were examined for their anti-bacterial activity by using well diffusion method. The standard cultures of S. aureus (Gram positive), B. subtilis (Gram positive), E. coli (Gram negative) and P. aeruginosa (Gram negative) were obtained from Department of Biotechnology, Dr. Ambedkar College, Nagpur. N-substituted benzoxazolyl benzamides and standard drug were dissolved in DMF to prepare stock solutions.
For the growth of bacterial colony Muller Hinton agar was used as the culture medium, that was prepared by using Beef Extract (2.00 gm), Acid Hydrolysate of Casein (17.50 gm), Starch (1.50 gm), Agar
(17.00 gm), in 1000 ml of distilled Water. The pH of agar medium was adjusted to 7.3 at 25ºC. Prepared agar medium was mixed well and autoclaved at 15 lbs pressure for at least 20 minutes, to sterilize the media. In the 100ml sterile medium single loop-full of micro-organisms were inoculated and incubated for 24 h at 37°C. This media were poured in petridishes slowly and allowed to solidify. Two well were created in the agar medium with the help of a borer of 6 mm diameter. Test samples/ standards (0.1 ml) was introduced into the well. All the plates were incubated at 37°C for 24 hours. The antibacterial activities of compounds were evaluated by measuring the zone of inhibition in mm. The diameter of the zone of inhibition for samples was measured and recorded Table 2.
Table 1. Physical properties and elemental analysis of N-{(1,3-benzo[d]thiazol-2yl)carbamothioyl}-2/4substituted benzamides 3a-g
Produ ct Code | R | Mol. formula | Mol. weight | Yiel d (%) | M.P.0C | Elemental composition: found (calculated) % | |||
---|---|---|---|---|---|---|---|---|---|
C | H | N | S | ||||||
3a | H | C15H11N3OS2 | 313.40 | 83 | 189 | 56.39 (57.49) | 3.49 (3.54 ) | 13.52 (13.41) | 20.49 (20.46) |
3b | 4-Cl | C15H10ClN3OS2 | 347.84 | 80 | 254 | 51.82 (51.79) | 2.88 (2.90) | 11.93 (12.08) | 18.56 (18.44) |
3c | 4-CH3 | C16H13N3OS2 | 327.42 | 78 | 199 | 58.81 (58.69) | 3.96 (4.00) | 12.68 (12.83) | 19.48 (19.59) |
3d | 4-OCH3 | C16H13N3O2S2 | 343.42 | 79 | 172 | 56.12 (55.96) | 3.78 (3.82) | 12.46 (12.24) | 17.98 (18.67) |
3e | 4-NO2 | C15H10N4O3S2 | 358.39 | 88 | 268 | 51.05 (50.27) | 3.07 (2.81) | 15.23 (15.63) | 16.71 (17.89) |
3f | 2-Cl | C15H10ClN3OS2 | 347.84 | 92 | 253 | 50.98 (51.79) | 3.02 (2.90) | 12.98 (12.08) | 17.96 (18.44) |
3g | 2-CH3 | C16H13N3OS2 | 327.42 | 77 | 214 | 57.89 (58.69) | 4.13 (4.00) | 13.15 (12.83) | 18.46 (19.59) |
Table 2: Antibacterial activity of N-(benzo[d]thiazol-2-ylcarbamothioyl)-2/4-substituted Benzamides 3a-g
Compound | (Zone of inhibition in mm at 100 µg/mL) | |||
---|---|---|---|---|
Gram-positive | Gram-negative | |||
S. aureus | B. subtilis | E. coli | P. aeruginosa | |
3a | 14 | 9 | 16 | 13 |
3b | 10 | 11 | 17 | - |
3c | 12 | 14 | 19 | 15 |
3d | 5 | - | 13 | 8 |
3e | 11 | 13 | 18 | 7 |
3f | - | 12 | 8 | 9 |
3g | 4 | - | 6 | 8 |
Standard Drug | 18 | 12 | 17 | 19 |
In the present work, we have reported synthesis ofN-{(1,3-benzo[d]thiazol-2-yl)carbamothioyl}-2/4substituted benzamides3a-gfrom 2-aminobenzothiazole1and benzoyl isothiocyanates 2a-g as presented in scheme 1.
2-Aminobenzothiazole1was synthesized by treatment of ammonium thiocyanate on aryl amine followed by bromination and then after basification with ammonium hydroxide by a known preparation method21.The yields of the respective 2-aminobenzothiazoles were found to be excellent. The 2
-1 -1
aminobenzothiazole showed characteristic peaks at 1257-1294 cmfor (C-S) , 1310-1434 cmfor (C-N), 1567
-1 -1 1
1625 cmfor (C=N), 3341 -3410 cmfor (NH) in FTIR spectral data. The H NMR spectra shows a broad singlet at 5.21 -6.28 ppm due to (–NH2)protons (D2O exchangeable) besides those for aromatic protons in the region 6.93 -8.24ppm. 2/4-Substituted benzoylisothiocyanates 2a-gwere obtained by reactingsubstituted
22 -1
benzoyl chlorides with ammonium thiocyanates. The FTIR bands showed band for (C=O) at 1682-1728 cmand (N-C-S) at 2125-2245 cm-1. The 1H-NMR sprectum showed multiplet at δ 7.19-8.39 for aromatic protons.
The target compounds N-{(1,3-benzothiazol-2-yl)amino]carbonothioyl}-2/4-substituted benzamides were synthesized by modified (less time and high yield) procedure23, the reaction was carried out in benzene-2propanol (5:1) mixture.Thus, interaction of 2-aminobenzothiazoles 1 with benzoyl isothiocyanates 2a-g gaveN{(1,3-benzo[d]thiazol-2-yl)carbamothioyl}-2/4-substituted benzamides3a-g in excellent yield (scheme I).
The structural elucidation of compounds was done through chemical tests, elemental (C, H, N and S) analysis and spectroscopic tools such as, FTIR, 1H NMR and mass spectroscopy. IR (KBr) spectra of the compound 3a-ghad strong absorptions at 3106.24-3036.74(aromatic C-H). It displayed absorptionband near
-1 -1
3407.94-3288.31cmcorresponds to presence of free N-H and 3401.16-3118.65cmfor associated N
−1 −1
H.Absorptions at 1681.14-1652.31cmand 1123.83-1052.13cmthat were assigned to C=O and C=S functions, respectively. In the IR spectrum of the3a-gpeaks of C=O stretching, -NH2bending and stretching indicated the presence of amide linkage.
The 1H-NMR data of 3a-g obtained in DMSO solution are given in the experimental section and are consistent with the structural results. The aromatic protons produced well-defined signals at δ 7.22-8.28, 1HNMR data confirmed presence of (NHC=O) and (NHC=S) by showing singlet at 8.17-9.86 and broad singlet at 12.28-13.05, respectively, exchangeable with D2O. The disappearance of the -NH2signal from the 1H NMR spectrum and the presence of singlet in the region of δ 12.28-13.05indicate that the -NH2group has been converted to amide linkage. Physical properties and elemental analysis of data for newly synthesized compounds are presented in Table 1.
In vitro biological activity: All the newly synthesized compounds 3a-g were tested for their antibacterial activity. It was determined well disk diffusion method at a concentration of 100mg/ml using DMF as a solvent against the different bacterial strains such as S. aureus, B. subtilis, E. coli and P. aeruginosa. The zone of inhibition of each strain was recorded shown in Table 2. The activity has been compared with known standard drug ampicillin and erythromycin. It can be observed that some of the newly synthesized compounds possess good to moderate antimicrobial activity as compared with standard drug.
Computational Studies:
Molinspiration is a web based software use to check the bioavailability of compounds. Physicochemical parameters of compounds play a vital role in generation and determination of bioactivity of any compound. It is use to evaluate the different parameters such as MiLogP, TPSA, Molecular weight, Molecular volume, Number of Hydrogen Bond Acceptors, Number of Hydrogen Bond Donors and Computed drug-likeness score.
MiLogP (octanal/water partition coefficient) has been calculated by the methodology develop by molispiration and calculated as sum of fragment-based contributions and corrections factors and used to predict the permeability of molecule across the cell membrane24(Table 3). Lipophilicity (log p value) is an important parameter which determines solubility, reactivity and degradation of drugs, prior reaching to a pharmacological target. PSA is another helpful parameter for the prediction of molecular transport properties. It may be defined as a sum of surface contributions of polar atoms (usually oxygens, nitrogens and attached hydrogens) in a molecule, Polar surface area (PSA) has been shown to be very good descriptor characterizing drug absorption, including intenstinal absorption, bioavailability, Caco-2 monolayers permeability and blood brain barrier
25-26
penetration. A methodology to calculate molecular polar surface area (TPSA) has been described by Ertl et al. as a sum of fragment contributions27. Therefore, log P and PSA values for compounds using molinspiration software programs were calculated and compared them with values obtained for standard drugs ampicillin.
Oral bioavailability is an important property under investigation in the drug discovery process. The molecular properties were calculated on the basis of molecular descriptor i.e. Lipinski’s rule of five (rule of thumb)28. In the rule-of-five model, compounds are considered likely to be well absorbed and orally active when they possess the following attributes-number of H-bond donars <5 (nitrogen or oxygen atoms with one or more hydrogen atoms), number of H-bond acceptors< 10 (nitrogen or oxygen atoms), molecular weight <500, cLogP <5, and number of rotatable bonds <10.
Lipinski’s rule of five identifies the molecular properties are important for a drug's pharmacokinetics in the human body: absorption, intenstinal permeability, distribution, metabolism, and excretion. Obtained results of various parameters (Milog P (partition coefficient), molecular weight, number of heavy atoms, number of hydrogen donor, number of hydrogen acceptor and number of violation, number of rotatable bonds, volume) for the isolated compounds 3a-g have been reported in Table 3 and compared with the standard drugs.
For all the compounds 3a-g, the calculated clogP values were around 3.54-4.25 (<5), which is the upper limit for the drugs to be able to penetrate through biomembranes according to Lipinski’s rules29. All of these compounds present good oral bioavailability. Compounds with optimal range lipophilicity might have increased chances of success in development. PSA is a common measure for the optimization of a drug's ability to permeate cells. Molecules with PSA values greater than 140 A0 or more are expected to exhibit poor intenstinal absorption30. Table 3 shows that all the compounds are well below this limit. It has to be kept in mind that log P and PSA values are only two important, but not sufficient criteria for prediction of oral absorption of a drug. Number of rotatable bonds measures molecular flexibility and is considered to be a very good descriptor of absorption and bioavailbility of drugs. All the compounds can easily bind to the receptor as n violatios = 0 for the given set of compounds. Two or more violations of the rule of five suggest the probability of problems in bioavailability. It is interesting to see that, all the synthesized compounds follows Lipinski’s rule of five. The positive results recorded confirm that more or less most of these compounds could be used as potential antibacterial agent after some modifications.
Table 3: Molinspiration calculationsa of synthesized compounds.
Compounds | MW | Milog P | TPSA | OH-NH | Bond rot. | n-violations | Vol | O-N |
---|---|---|---|---|---|---|---|---|
a | 313.41 | 3.58 | 54.02 | 2 | 4 | 0 | 257.65 | 4 |
b | 347.85 | 4.25 | 54.02 | 2 | 4 | 0 | 271.19 | 4 |
c | 327.43 | 4.03 | 54.02 | 2 | 4 | 0 | 274.21 | 4 |
d | 343.43 | 3.63 | 63.25 | 2 | 5 | 0 | 283.19 | 5 |
e | 358.40 | 3.54 | 99.84 | 2 | 5 | 0 | 280.98 | 7 |
f | 347.85 | 4.21 | 54.02 | 2 | 4 | 0 | 271.19 | 4 |
g | 327.43 | 3.98 | 54.02 | 2 | 4 | 0 | 274.21 | 4 |
Ampicillin | 349.41 | -0.87 | 112.73 | 4 | 4 | 0 | 298.86 | 7 |
aMW, molecular weight; TPSA, total polar surface area; OH-NH, OH-NH interactions; nviolations, number of violations; Vol, Volume; ON, O-N interactions
Table 4: Drug likenessa of newly synthesized compounds
Compounds | GPCRL | ICM | KI | NRL | PI | EI |
---|---|---|---|---|---|---|
a | -0.63 | -0.63 | -0.30 | -0.94 | -0.64 | -0.22 |
b | -0.58 | -0.61 | -0.29 | -0.90 | -0.62 | -0.25 |
c | -0.63 | -0.68 | -0.32 | -0.91 | -0.64 | -0.28 |
d | -0.59 | -0.66 | -0.29 | -0.83 | -0.59 | -0.26 |
e | -0.67 | -0.61 | -0.38 | -0.89 | -0.64 | -0.32 |
f | -0.59 | -0.62 | -0.31 | -0.87 | -0.68 | -0.29 |
g | -0.61 | -0.70 | -0.31 | -0.87 | -0.63 | -0.27 |
Ampicillin | 0.04 | -0.47 | -0.71 | -0.61 | 0.87 | 0.25 |
aGPCRL, GPCR ligand; ICM, Ion channel modulator; KI, Kinase inhibitor; NRL, Nuclear receptor ligand; PI; Protease inhibitor and EI, Enzyme inhibitor
A material is considered bioactive if it has interaction with or effect on any cell tissue in the human body, pharmacological activity is usually taken to describe beneficial effects, i.e. the effects of drug candidates as well as a substance's toxicity. The bioactivity scores synthesized compounds 3a-g were assessed on the basis of (GPCR ligands, kinase inhibitors KI, ion channel modulators ICM, enzymes inhibitor EI, Protease inhibitor PI and nuclear receptors NRL) and are valued in Table 4. The bioactivity score for GPCR ligand is found to be -0.58 to -0.67, for ion channel modulator activity is -0.61 to-0.70. Similar results are obtained for kinase inhibition showed score -0.29 to -0.38. Bioactivity scores for nuclear receptor ligand, protease inhibitor and enzyme inhibition was found to be in the range. It indicated the probability of good to moderate activity towards GPCR ligands, ion channel modulators, kinase inhibitors, nuclear receptor ligands, protease inhibitors and other enzyme targets.These scores for organic molecules can be interpreted as active (bioactivity score > 0), moderately active (bioactivity score: -5.0-0.0) and inactive (bioactivity score <-5.0)31.All compounds have consistent negative values in all categories and numerical are even more negative than of standard drugs used for comparison. Therefore, it is readily seen that all the compounds are expected to have similar activity to standard drugs used based upon these six criteria. The compounds showed similar bioactivity scores on comparison with standards taken for the study. It indicates the molecules were active towards drug target.
We have efficiently synthesized series of novel N-{(1,3-benzo[d]thiazol-2-ylcarbamothioyl)-2/4substituted benzamides3a-g from 2-aminobenzothiazole in good to excellent yields. All the compounds were characterized using spectroscopic and analytical tools. Some of final products were screened for their antibacterial activity and it was observed that some of the compounds are having moderate to potent anti bacterial activity which is compared with standard drug.
We greatly acknowledge to The Principal and the Head of Department of Applied Chemistry, Shri Ramdeobaba College of Engineering and Management, Nagpur for their support for laboratory facilities.
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