identifier	taxonID	type	CVterm	format	language	title	description	additionalInformationURL	UsageTerms	rights	Owner	contributor	creator	bibliographicCitation
03FB8795FF82BD495E50B9D7E2201FC8.text	03FB8795FF82BD495E50B9D7E2201FC8.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Turbinaria conoides (J. Agardh) Kutzing	<div><p>2.4. Bioactive potential of the conoidecyclics isolated from T. conoides</p> <p>Conoidecyclic A exhibited dual attenuation property against inducible inflammatory enzymes COX-2 and 5-LOX (IC 50 1.75 and 4.24 mM, respectively). The anti-inflammatory activities of conoidecyclic A were higher than those displayed by conoidecyclic B (IC 50&gt; 1.9 mM) and conoidecyclic C (IC 50 5-LOX 5.07 mM) (Table 2). The anti-inflammatory selectivity index (SI) was greater for conoidecyclic A (1.79) than those displayed by conoidecyclic B and C (1.65–1.68) as well as synthetic anti-inflammatory agents (ibuprofen, 0.44 and sodium salicylate, 0.73) (Table 2). The lesser selectivity ratio of synthetic anti-inflammatory agents specified the selective inhibition towards COX-1, leading to several side effects (Laneuville et al., 1994). Therefore, it could possibly be concluded that conoidecyclic A, with higher SI and greater specificity towards COX-2 was noteworthy towards the development of selective anti-inflammatory therapeutic lead (Spangler, 1996). Conoidecyclic A exhibited significantly greater attenuation properties against ACE-I and PTP-1B (IC 50 1.23 and 1.39 mM, respectively) as compared to other studied conoidecyclics (IC 50&gt; 1.80 mM) (Table 2). The radical scavenging activities (IC 50DPPH 1.20 and IC 50ABTS 1.48 mM) exhibited by conoidecyclic A were greater compared to those displayed by conoidecyclic B (IC 50 1.35–1.54 mM), conoidecyclic C (IC 50 1.54–1.81 mM) and commercially available standards (IC 50 1.46–1.69 mM).</p> <p>Different superscripts (P–V) indicate the standards used for different activities; P- α -Tocopherol; Q-Butylated hydroxy toluene; Ib-Ibuprofen; S-Sodium salicylate; CP- Captopril; SV- Sodium metavandate.</p> <p>a Bioactivities were expressed as IC values (mM). Samples were analyzed in triplicate (n = 3) and expressed as mean ± standard deviation. Means followed by the 50 different superscripts (a-e) within the same row indicated significant differences (P &lt;0.05).</p> <p>b Selectivity index has been calculated as the ratio of anti COX-1(IC) to that of anti COX-2(IC).</p> <p>50 50 c Structure-activity relationship analysis was carried out by using different molecular descriptors of the purified compounds as described in the text. tPSA, topological polar surface area; MV, molar volume; P, parachor; MR, molar refractivity; Log POW, logarithmic scale of the octanol-water partition coefficient; PI, polarizability.</p> <p>2.5. Structure-activity correlation study analysis of conoidecyclic analogues isolated from T. conoides</p> <p>The steric factors of the studied compounds might play pivotal roles towards their potential bioactivities. Notably, the electronic properties of conoidecyclic B and C were higher than those of conoidecyclic A (Table 2), even though the bioactivities of the latter were greater. This could be explained by the comparatively lesser steric bulkiness of conoidecyclic A (P 1092.7 cm 3, MV 447.4 cm 3) than those recorded for conoidecyclic B (P 1316.5 cm 3, MV 534.9 cm 3) and C (P 1198.4, MV 522.0 cm 3) owing to the presence of bulkier side chain in the latter. These inferences were appropriately corroborated by the efficiency of conoidecyclic A towards the conformationally favorable interaction with the active binding sites of the target enzymes. Notably, the hydrophobicity of conoidecyclic A and B (log POW 3.13–3.83) were found to reside within the permissible limit of hydrophobic-lipophilic threshold (Lipinski, 2004), which could attribute to their prospective bioactive properties. An earlier report of literature inferred that the effective permeability in the cellular network (through inter membrane barrier) along with the radical scavenging activities of the pharmacophore agents might result in their potential bioactivities (Ishige et al., 2001).</p> <p>2.6. ADME and other physicochemical parametrs</p> <p>Swiss ADME tools were used (Daina et al., 2017) for the estimation of different physicochemical parameters, drug-likeness, solubilities and ADME behaviors of the isolated compounds (conoidecyclics A-C). Based upon the specific physicochemical parameters, the qualitative prediction was performed, and only conoidecyclic A passed the filter of Lipinski’ s rule without any violation, whereas conoidecyclic B and C had one violation (MW&gt; 500) (Table 3). Therefore, conoidecyclic A could possess greater oral bioavailability. Notably, all the three compounds could pass the filter of Veber rule without any violations (Table 3) (Daina et al., 2017). In addition to that, predicted bioavailability score for the studied compounds were comparable (0.55) with that of ibuprofen (0.55), which apparently recognized at least 10% oral bioavailability in rat and permeability towards Caco-2 cell lines (Daina et al., 2017) (Table 3). For the rapid estimation of drug-likeness, the bioavailability radar plot was adopted, and six physicochemical parameters (size, lipophilicity, polarity, flexibility, solubility and saturation) were taken into account (Fig. S34). The optimum range for each parameter was shown by a pink area. Evidently, conoidecyclic B and C displayed a deviation including larger size (MW&gt; 500), even though no eccentricity was apparent for conoidecyclic A, and all the six values (comparing to ibuprofen, conoidecyclic A exhibited lesser flexibility) led to optimal physicochemical attributes leading to an acceptable oral bioavailability. Solubility is considered to be one of the vital parameters for drug development activities, and also related to absorption (Daina et al., 2017). Estimated aqueous solubility (Log S; ESOL and SILICOS-IT) for three isolated compounds based on molecular structure were in a range of moderately soluble to soluble (Table 3). Logarithm value of skin permeability coefficient Kp (regarding pharmacokinetics) was calculated for the isolated compounds including the standard (ibuprofen), whereas more negative value of Kp inferred lesser skin permeability. The latter could be linearly correlated with the molecular size, lipophilicity, and it was observed that conoidecyclic A exhibited a Kp value (- 6.51 cm /s) closer to that exhibited by conoidecyclic B and C (- 6.56 and - 7.25 cm /s, respectively) (Table 3).</p> <p>2.7. Kinetic properties of ACE-I, PTP-1B and 5- LOX inhibition</p> <p>Kinetic studies were performed to determine the mode of inhibition of conoidecyclics A-C, and the inhibition constants (Ki) were determined by Lineweaver-Burk and Dixon plots. Conoidecyclics were found to inhibit ACE-I, PTP-1B and 5- LOX enzymes, in a non-competitive fashion as determined by the Lineweaver-Burk plot (Fig. S35). Increase of substrate concentrations could result in non-intersect series of line on Y-axis in the Lineweaver-Burk plot (Fig. S35) but intersected on the negative X axis (Ki) in the Dixon plots (Fig. 6). Conoidecyclic A exhibited lesser inhibition constant towards inhibition of ACE-I (1.1 mM), PTP-1B (1.2 mM) and 5- LOX (4.0 mM) than those displayed by other studied metabolites (Fig. 6). An inverse relation of Vmax with various concentrations of conoidecyclics A-C inferred the non-competitive inhibition of the target enzymes (Blat, 2010). Among the studied metabolites, conoidecyclic A exhibited lesser apparent Vmax (0.31–0.14, 0.29–0.17 and 0.32–0.17 ΔA min 1 for ACE-I, PTP-1B and 5- LOX inhibition, respectively) (Table S2) than other studied macrolides, which implied that the former could efficiently bind with targeted enzyme to diminish the reaction velocity.</p> <p>a TPSA = Topological polar surface area.</p> <p>b Log P= The partition coefficient between n-octanol and water.</p> <p>o/w c Log S = The decimal logarithm of the molar solubility in water.</p> <p>d Lipinski criteria range are, lipophilicity (Log P) ≤ 5, MW ≤ 500, H-bond o/w donors ≤ 5 and H-bond acceptors ≤ 10.</p> <p>e Ghose filter criteria range are, Log Pin 0.4 to +5.6 range, MR from 40 to o/w 130, MW from 180 to 480, No. of atoms from 20 to 70.</p> <p>f Veber rule criteria range are, RB ≤ 10 and TPSA ≤140 Å 2.</p> <p>g Log K= skin permeability coefficient.</p> <p>p</p> <p>2.8. In silico molecular modeling analysis of conoidecyclics isolated from T. conoides</p> <p>The macrocyclic derivatives (conoidecyclics A-C) were subjected to in-silico molecular modeling studies against pro-inflammatory 5- LOX and COX-2 enzymes, and the results were obtained with the help of RMSD data. Conoidecyclic A, on molecular modeling with COX-2 and ACE-I exhibited three hydrogen bonding interactions with the enzyme active site, whereas five hydrogen bonds were apparent between the ligand and the active site amino acyl residues of PTP-1B (Fig. 3, Table 4). In comparison, conoidecyclic B and C exhibited lesser number of hydrogen bonding interactions with the active site of targeted enzymes (Figs. 4–5, Table 4). Likewise, conoidecyclic A recorded least binding energy (13.34, 14.51, 13.87 and 11.27 kcal mol 1 with 5- LOX, COX-2, PTP-1B and ACE-I respectively) and docking score (~ 12 to 15 kcal mol 1) than those displayed by conoidecyclics B and C (Table 4). Likewise, the constant of enzyme inhibition, Ki upon interaction with COX-2 and 5- LOX were lesser for conoidecyclic A (23.20 and 33.23 pM, respectively) followed by those of conoidecyclic B and C (Table 4). The lowest docking score as well as binding energy of conoidecyclic A described its greater attenuation potential against 5- LOX and COX-2 enzymes, which were reported to produce inflammatory prostaglandins (PGE 2, PGG 2, PGI 2, PGF 2 etc), thromboxane (TXA 2) and leukotrienes (such as LTB 4) causing the development of inflammation (Hanna and Hafez, 2018).</p></div> 	https://treatment.plazi.org/id/03FB8795FF82BD495E50B9D7E2201FC8	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Chakraborty, Kajal;Dhara, Shubhajit	Chakraborty, Kajal, Dhara, Shubhajit (2021): Conoidecyclics A-C from marine macroalga Turbinaria conoides: Newly described natural macrolides with prospective bioactive properties. Phytochemistry (112909) 191: 1-14, DOI: 10.1016/j.phytochem.2021.112909, URL: http://dx.doi.org/10.1016/j.phytochem.2021.112909
03FB8795FF8EBD475D06BE59E37419F2.text	03FB8795FF8EBD475D06BE59E37419F2.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Turbinaria conoides (J. Agardh) Kutzing	<div><p>4.3. Chromatographic purification of organic extract of T. conoides</p> <p>The solvent extract of T. conoides (30 g) was fractionated by sequential chromatographic procedures. The crude was mixed with the silica gel (60–120 mesh, 3.0 g) and loaded into a column of glass (0.1 m × 40 mm) with silica gel (60–120 mesh, 50 g). The elution was initiated with less polar solvent (n -hexane), followed by an increase of polarity (EtOAc to MeOH) to collect twenty-five fractions (10 mL/fraction), which were combined to five (TC 1 through TC 5) (Table S1) based upon TLC (8:2 v/v, n -hexane:EtOAc) and RP C 18 -HPLC (MeOH/acetonitrile MeCN, 3:2 v/v) analysis, and those fractions (TC 1 -TC 5) were assessed for their bioactivities. The fractions possessing potential bioactive properties were chosen for further purification. The fractions TC 3 (EtOAc: n - hexane 2:3 v/v; 4.65 g, 15.5% yield) and TC 4 (EtOAc: n -hexane 7:3 v/v; 4.26 g, 14.2% yield) displayed greater attenuation potential against COX-2 and 5-LOX enzymes. The radical scavenging potential of TC 3 and TC 4 against 1,1-diphenyl-2-picryl-hydrazil (DPPH) and 2, 2 ′ -azino-bis-3- ethylbenzothiozoline-6-sulfonic acid (ABTS +) were found to be greater compared to others (Table S1), and therefore, were selected for downstream purification. Likewise, the sub-fraction TC 3 was subjected to fractionation on a silica gel (230–400 mesh) loaded glass column (450 mm × 30 mm). Step-wise gradient elution with n -hexane-EtOAc (9:1 to 3:2, v/v) yielded twenty sub-fractions (20 mL/fraction), which were combined to four (TC 3-1 -TC 3-4) after TLC (n -hexane-EtOAc, 4:1 v/v) and RP-C 18 HPLC (MeOH–MeCN, 3:2 v/v) experiments. The fraction TC 3-4 (1.19 g, 3.96% yield) eluted at n -hexane-EtOAc (6:4, v/v) displayed potential bioactivities (Table S1). Therefore, TC 3-4 was further subfractionated on fine silica gel (SP 1 –B 1A, 230–400 mesh, 12 g) loaded into a column connected to the flash chromatography system (SP 1 –B 1A, Biotage, Sweden) by increasing gradient of n -hexane/EtOAc/MeOH to acquire twelve sub-fractions (15 mL/fraction). The latter fractions were combined to three (TC 3-4-1 -TC 3-4-3) after TLC (n -hexane-EtOAc, 8:2 v/v) and RP-C 18 HPLC (MeOH/MeCN, 3:2 v/v). TC 3-4-1 (0.768 g, 2.56% yield) was purified on silica gel GF 254 by n -hexane: EtOAc (25:1, v/v) solvent system using the preparatory TLC (PTLC) system to yield conoidecyclic A (85 mg, 0.28%, based on dry weight) and conoidecyclic B (73 mg, 0.24%, based on dry weight), and their homogeneity was confirmed by TLC (EtOAc/ n -hexane, 1:9 v/v) and RP-C 18 HPLC (MeOH/ MeCN, 3:2 v/v). The fraction TC 4 was subjected to flash chromatography on a silica gel column (230–400 mesh) with a gradient elution of n -hexane/EtOAc/MeOH to yield sixteen fractions (15 mL/fraction), which were combined into three (TC 4-1 -TC 4-3) after TLC (EtOAc- n -hexane, 1:4 v/v). TC 4-2 (1.15 g, 3.83% yield) displayed greater bioactive potential than other column sub-fractions (Table S1), and flash chromatographic separation using a gradient elution of n -hexane/EtOAc yielded eleven fractions (13 mL/fraction), which were combined into three (TC 4-2-1 -TC 4-2-3). The bioactive fraction TC 4-2-3 (0.442 g, 1.47% yield) was a mixture, and was further purified by PTLC (EtOAc: n -hexane, 1:26, v/v) to obtain conoidecyclic C (65 mg, 0.22%, based on dry weight). The homogeneity of the latter was confirmed by RP-C 18 HPLC (MeOH–MeCN 3:2, v/v) and TLC (EtOAc/ n -hexane 1:4, v/v).</p> </div>	https://treatment.plazi.org/id/03FB8795FF8EBD475D06BE59E37419F2	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Chakraborty, Kajal;Dhara, Shubhajit	Chakraborty, Kajal, Dhara, Shubhajit (2021): Conoidecyclics A-C from marine macroalga Turbinaria conoides: Newly described natural macrolides with prospective bioactive properties. Phytochemistry (112909) 191: 1-14, DOI: 10.1016/j.phytochem.2021.112909, URL: http://dx.doi.org/10.1016/j.phytochem.2021.112909
