Id |
Subject |
Object |
Predicate |
Lexical cue |
T199 |
0-63 |
Sentence |
denotes |
In-silico drug-likeness and pharmacokinetic property prediction |
T200 |
64-201 |
Sentence |
denotes |
All the structures used for docking were analysed for in silico drug-likeness based on the Lipinski’s rules using pkCSM server (Table 4). |
T201 |
202-358 |
Sentence |
denotes |
The lipophilicity (expressed as LogP) predicted for all the compounds were found to be well above the traditionally cut-off value of 5 used for drug design. |
T202 |
359-512 |
Sentence |
denotes |
Curcumin and its derivatives, used in this study, show suitable MW values (MW < 500) essential for a successful penetration through biological membranes. |
T203 |
513-639 |
Sentence |
denotes |
The surface area (SA) for all the compounds was observed to be in the range 115.89 − 240.65 Å2 which is well within the limit. |
T204 |
640-897 |
Sentence |
denotes |
All compounds, except 5-di-tert-butyl-4-hydroxybenzaldehyde curcumin (BHBC), 4-methoxy-1-naphthaldehyde curcumin (MNC), Syringaldehyde curcumin (SYC) and compound-16, fall into the appropriate range indicating good bioavailability of the candidate molecule. |
T205 |
898-1042 |
Sentence |
denotes |
The number of hydrogen bond acceptors (HBA, ≤10) and donors (HBD, ≤5) for all the compounds were in accordance with the Lipinski’s rule of five. |
T206 |
1043-1051 |
Sentence |
denotes |
Table 4. |
T207 |
1053-1119 |
Sentence |
denotes |
In-silico prediction of drug-likeness for curcumin derivatives[a]. |
T208 |
1120-1182 |
Sentence |
denotes |
Compound MW LogP SA HBA HBD nviolations Rotatable bonds |
T209 |
1183-1220 |
Sentence |
denotes |
BHBC 534.78 8.93 236.0 4 3 1 6 |
T210 |
1221-1259 |
Sentence |
denotes |
MNC 538.59 6.14 232.11 7 2 1 11 |
T211 |
1260-1298 |
Sentence |
denotes |
BDMC 308.33 3.83 133.51 4 3 5 |
T212 |
1299-1335 |
Sentence |
denotes |
1 270.353 4.21 115.89 3 1 4 |
T213 |
1336-1372 |
Sentence |
denotes |
2 332.739 3.79 136.57 5 4 4 |
T214 |
1373-1409 |
Sentence |
denotes |
3 314.337 3.77 133.64 5 4 4 |
T215 |
1410-1445 |
Sentence |
denotes |
4 322.36 4.36 139.56 3 3 4 |
T216 |
1446-1482 |
Sentence |
denotes |
5 364.441 4.93 159.62 4 0 5 |
T217 |
1483-1519 |
Sentence |
denotes |
6 320.388 4.95 141.45 4 3 1 |
T218 |
1520-1555 |
Sentence |
denotes |
7 325.32 3.60 138.02 5 1 6 |
T219 |
1556-1592 |
Sentence |
denotes |
8 329.193 4.45 125.75 2 1 4 |
T220 |
1593-1629 |
Sentence |
denotes |
9 462.181 5.24 164.71 7 2 0 |
T221 |
1630-1667 |
Sentence |
denotes |
10 351.358 4.13 149.74 4 5 1 |
T222 |
1668-1705 |
Sentence |
denotes |
11 360.375 5.07 149.89 2 1 3 |
T223 |
1706-1743 |
Sentence |
denotes |
12 419.565 6.24 185.40 9 4 1 |
T224 |
1744-1781 |
Sentence |
denotes |
13 389.495 5.22 171.67 4 4 1 |
T225 |
1782-1819 |
Sentence |
denotes |
14 342.778 3.81 143.82 4 2 2 |
T226 |
1820-1857 |
Sentence |
denotes |
15 469.629 4.38 208.20 6 5 1 |
T227 |
1858-1896 |
Sentence |
denotes |
16 486.564 6.19 211.58 11 6 1 0 |
T228 |
1897-1935 |
Sentence |
denotes |
DMC 342.391 3.20 146.43 5 2 9 |
T229 |
1936-1974 |
Sentence |
denotes |
FAC 550.604 4.7 232.81 9 2 15 |
T230 |
1975-2014 |
Sentence |
denotes |
IBC 556.655 5.24 240.62 7 1 15 |
T231 |
2015-2054 |
Sentence |
denotes |
IVC 504.535 4.69 214.22 8 3 11 |
T232 |
2055-2094 |
Sentence |
denotes |
SYC 430.453 3.77 180.12 10 8 1 3 |
T233 |
2095-2310 |
Sentence |
denotes |
[a] MW = Molecular weight, LogP = octanol-water partition coefficient, SA = Surface Area, HBA = Number of hydrogen bond acceptor, HBD = Number of hydrogen bond donor, nviolations = violations from Lipinski’s rule. |
T234 |
2311-2316 |
Sentence |
denotes |
BHBC: |
T235 |
2317-2371 |
Sentence |
denotes |
3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin, MNC: |
T236 |
2372-2414 |
Sentence |
denotes |
4-methoxy-1-naphthaldehyde curcumin, BDMC: |
T237 |
2415-2443 |
Sentence |
denotes |
Bis-demethoxy curcumin, DMC: |
T238 |
2444-2468 |
Sentence |
denotes |
Demethoxy curcumin, FAC: |
T239 |
2469-2496 |
Sentence |
denotes |
Ferulic-acid curcumin, IBC: |
T240 |
2497-2521 |
Sentence |
denotes |
Ibuprofen curcumin, IVC: |
T241 |
2522-2548 |
Sentence |
denotes |
Isovanillin curcumin, SYC: |
T242 |
2549-2573 |
Sentence |
denotes |
Syringaldehyde curcumin. |
T243 |
2574-2729 |
Sentence |
denotes |
Additionally, a variety of key ADMET (Absorption, Distribution, Metabolism and Excretion) properties have also been calculated with the aid of pkCSMserver. |
T244 |
2730-2764 |
Sentence |
denotes |
The results are listed in Table 5. |
T245 |
2765-3067 |
Sentence |
denotes |
All curcumin derivatives showed moderate to high water solubility ranging from −2.91 log mol/L (BHBC) to −6.99 log mol/L (compound-12), in addition to high Caco-2 permeability (permeation > 0.90) except compound BHBC and MNC (permeation = 0.67 and 0.43 respectively) which showed moderate permeability. |
T246 |
3068-3191 |
Sentence |
denotes |
Intestinal absorption (IA) has been found to be greater than 85% indicating good permeation across the intestinal membrane. |
T247 |
3192-3280 |
Sentence |
denotes |
Further, all curcumin compounds showed good permeation through skin (permeation > −2.5). |
T248 |
3281-3515 |
Sentence |
denotes |
Additionally, all curcumin compounds showed no inhibition towards P-glycoprotein I and P-glycoprotein II, except compounds BHBC, MNC, compound-13 and Ferrulic acid curcumin (FAC) which demonstrated inhibition towards P-glycoprotein I. |
T249 |
3516-3653 |
Sentence |
denotes |
Furthermore, all curcumin compounds showed poor BBB permeability and moderate CNS permeability except Isovanillin curcumin (IVC) and SYC. |
T250 |
3654-3827 |
Sentence |
denotes |
All showed inhibition towards the metabolizing enzyme CYP3A4 except BHBC, compounds-8, -11, -14, -15 and -16, while except compound-15, all showed inhibition towards CYP2C9. |
T251 |
3828-3980 |
Sentence |
denotes |
All curcumin derivatives were found to show the total clearance in the range 0.10 log mL/min/kg (compound-1 and -4) to 1.01 log mL/min/kg (compound-15). |
T252 |
3981-4189 |
Sentence |
denotes |
Further, all curcumin derivatives except compound 15 were found to act as OCT2 substrate, thus indicating that these compounds will not have any adverse interactions and no negative effect on renal clearance. |
T253 |
4190-4198 |
Sentence |
denotes |
Table 5. |
T254 |
4200-4254 |
Sentence |
denotes |
In-silico ADME prediction for curcumin derivatives[a]. |
T255 |
4255-4308 |
Sentence |
denotes |
Comp Absorption Distribution Metabolism Excretion |
T256 |
4309-4376 |
Sentence |
denotes |
WS CP IA SP PI-1 PI-2 VD FU BBB CNS CI-1 CI-2 TC RS |
T257 |
4377-4464 |
Sentence |
denotes |
BHBC –2.91 0.67 88.62 –2.73 Yes Yes –0.39 0.31 –0.67 –0.85 No Yes 0.15 No |
T258 |
4465-4550 |
Sentence |
denotes |
MNC –3.64 0.43 100 –2.73 Yes Yes –1.45 0.33 –0.39 –2.73 Yes Yes 0.26 No |
T259 |
4551-4637 |
Sentence |
denotes |
BDMC –4.43 1.01 95.92 –2.99 No No –0.22 0.08 –0.72 –2.11 Yes Yes 0.12 No |
T260 |
4638-4719 |
Sentence |
denotes |
1 –4.66 1.25 91.80 –2.51 No No 0.18 0.06 0.01 –1.45 Yes Yes 0.10 No |
T261 |
4720-4803 |
Sentence |
denotes |
2 –3.23 0.93 89.16 –2.76 No No –0.07 0.12 –1.07 –2.29 Yes Yes 0.05 No |
T262 |
4804-4887 |
Sentence |
denotes |
3 –3.19 0.94 89.70 –2.76 No No –0.02 0.13 –1.06 –2.27 Yes Yes 0.06 No |
T263 |
4888-4967 |
Sentence |
denotes |
4 –4.11 0.92 87.64 –3.07 No No 0.09 0 –0.74 –1.85 Yes Yes 0.10 No |
T264 |
4968-5047 |
Sentence |
denotes |
5 –6.39 1.06 94.85 –2.49 No No 0.25 0 –0.03 –1.30 Yes Yes 0.22 No |
T265 |
5048-5127 |
Sentence |
denotes |
6 –5.42 1.43 90.49 –2.73 No No 0.05 0 –0.33 –1.29 Yes Yes 0.23 No |
T266 |
5128-5207 |
Sentence |
denotes |
7 –4.54 1.04 91.97 –2.73 No No –0.37 0 0.28 –2.20 Yes Yes 0.13 No |
T267 |
5208-5285 |
Sentence |
denotes |
8 –5.09 1.66 90.44 –2.29 No No 0.27 0 0.16 –1.47 No Yes 0.14 No |
T268 |
5286-5364 |
Sentence |
denotes |
9 –7.03 1.13 93.34 –2.51 No No 0.37 0 0.46 –1.26 Yes Yes 0.26 No |
T269 |
5365-5446 |
Sentence |
denotes |
10 –4.89 0.94 91.50 –2.74 No No –0.04 0 –0.24 –1.93 Yes Yes 0.11 No |
T270 |
5447-5525 |
Sentence |
denotes |
11 –5.93 1.28 89.16 –2.59 No No 0.36 0 0.66 –1.40 No Yes 0.13 No |
T271 |
5526-5606 |
Sentence |
denotes |
12 –6.99 1.02 91.30 –2.75 No No 0.66 0 –0.32 –1.85 Yes Yes 1.04 No |
T272 |
5607-5689 |
Sentence |
denotes |
13 –5.42 1.27 92.76 –2.80 Yes Yes 0.54 0 –0.02 –1.58 Yes Yes 0.26 No |
T273 |
5690-5773 |
Sentence |
denotes |
14 –4.20 1.12 90.31 –2.92 No No –0.04 0.01 –0.31 –1.33 No Yes 0.08 No |
T274 |
5774-5856 |
Sentence |
denotes |
15 –3.76 0.97 88.86 –2.79 No No 1.90 0.16 –0.20 –1.26 No No 1.01 Yes |
T275 |
5857-5940 |
Sentence |
denotes |
16 –6.92 0.90 94.67 –2.73 No No –0.59 0.07 –0.72 –2.62 No Yes 0.41 No |
T276 |
5941-6026 |
Sentence |
denotes |
DMC –3.95 0.99 92.03 –2.74 No No –0.06 0.12 –0.23 –2.66 Yes Yes 0.32 No |
T277 |
6027-6114 |
Sentence |
denotes |
FAC –4.02 1.41 83.68 –2.76 Yes Yes –0.58 0.24 –0.91 –3.26 Yes Yes 0.55 No |
T278 |
6115-6200 |
Sentence |
denotes |
IBC –4.36 0.91 91.72 –2.73 No No –0.88 0.18 –0.53 –2.77 Yes Yes 0.62 No |
T279 |
6201-6286 |
Sentence |
denotes |
IVC –3.95 0.96 89.31 –2.73 No No –0.60 0.24 –1.37 –3.02 Yes Yes 0.16 No |
T280 |
6287-6371 |
Sentence |
denotes |
SYC –3.89 1.01 89.15 –2.73 No No 0.28 0.17 –1.47 –3.14 Yes Yes 0.23 No |
T281 |
6372-6889 |
Sentence |
denotes |
[a] Abbreviations: WS—Water solubility (log mol/L), CP—Caco2 permeability (log Papp in 10-6 cm/s), IA—Human intestinal absorption (% Absorbed), SP—Skin permeability (log Kp),PI-1—P-glycoprotein I inhibitor, PI-2—P-glycoprotein II inhibitor, VD—Human volume ofdistribution (log L/kg), FU—Fraction unbound (human) (Fu), BBB—BBB permeability (logBB), CNS—CNS permeability (log PS), CI-1—CYP3A4 inhibitor, CI-2—CYP2C9 inhibitor,TC—Total clearance (log mL/min/kg), RS—Renal OCT2 (organic cation transporter 2) substrate. |
T282 |
6890-6895 |
Sentence |
denotes |
BHBC: |
T283 |
6896-6950 |
Sentence |
denotes |
3-5-di-tert-butyl-4-hydroxybenzaldehyde curcumin, MNC: |
T284 |
6951-6993 |
Sentence |
denotes |
4-methoxy-1-naphthaldehyde curcumin, BDMC: |
T285 |
6994-7022 |
Sentence |
denotes |
Bis-demethoxy curcumin, DMC: |
T286 |
7023-7047 |
Sentence |
denotes |
Demethoxy curcumin, FAC: |
T287 |
7048-7075 |
Sentence |
denotes |
Ferulic-acid curcumin, IBC: |
T288 |
7076-7100 |
Sentence |
denotes |
Ibuprofen curcumin, IVC: |
T289 |
7101-7127 |
Sentence |
denotes |
Isovanillin curcumin, SYC: |
T290 |
7128-7152 |
Sentence |
denotes |
Syringaldehyde curcumin. |