Browsing by Author "Paul, Atish Tulshiram"

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Antimicrobial Resistance Underlying Mechanisms and Therapeutic Approaches
(Springer, 2022) Paul, Atish Tulshiram
Describes the mechanisms of AMR in hospital settings, agriculture, livestock and other environments
Apoptosis inducing activity of steroidal constituents from Solanum xanthocarpum and Asparagus racemosus
(Elsevier, 2010-08) Paul, Atish Tulshiram
A series of Sarsapogenin and Diosgenin derived steroidal constituents (1-12), isolated from Solanum xanthocarpum and Asparagus racemosus were screened for their ability to induce cell death and apoptosis of colon carcinoma cells. The carbohydrate moieties linked to the steroid backbones were found to strongly influence cytotoxic activity and cell death mode (apoptosis or necrosis). Compound 10, from A. racemosus was found to be a potent inducer of apoptosis.
Biaryl carboxamide-based peptidomimetics analogs as potential pancreatic lipase inhibitors for treating obesity
(Wiley, 2024-01) Kumar, Gautam; Paul, Atish Tulshiram
A series of 1,1′-biphenyl-3-carboxamide and furan-phenyl-carboxamide analogs were synthesized using an optimized scheme and confirmed by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry techniques. The synthesized peptidomimetics analogs were screened in vitro to understand the inhibitory potential of pancreatic lipase (PL). Analogs were assessed for the PL inhibitory activity based on interactions, geometric complementarity, and docking score. Among the synthesized analogs, 9, 29, and 24 were found to have the most potent PL inhibitory activity with IC50 values of 3.87, 4.95, and 5.34 µM, respectively, compared to that of the standard drug, that is, orlistat, which inhibits PL with an IC50 value of 0.99 µM. The most potent analog, 9, exhibited a competitive-type inhibition with an inhibition constant (Ki) of 2.72 µM. In silico molecular docking of analog 9 with the PL (PDB ID:1LPB) showed a docking score of −11.00 kcal/mol. Analog 9 formed crucial hydrogen bond interaction with Ser152, His263, π–cation interaction with Asp79, Arg256, and π–π stacking with Phe77, Tyr114 at the protein's active site. The molecular dynamic simulation confirmed that analog 9 forms stable interactions with PL at the end of 200 ns with root mean square deviation values of 2.5 and 6 Å. No toxicity was observed for analog 9 (concentration range of 1–20 µM) when tested by MTT assay in RAW 264.7 cells.
Bis-indole alkaloids from Tabernaemontana divaricata as potent pancreatic lipase inhibitors: molecular modelling studies and experimental validation
(Springer, 2017-03) Paul, Atish Tulshiram
Obesity is the major leading cause of global mortality among metabolic disorders. Orlistat, a pancreatic lipase inhibitor, is the only approved drug of choice for the long term treatment of obesity. However, recent findings reported severe adverse effects with long term administration of orlistat. Plant-based natural products represent a vast reservoir of chemical entities that have the potential to treat various metabolic disorders. In the present study, we have performed a preliminary screening of local flora for pancreatic lipase inhibition assay, which highlighted the methanol extract of Tabernaemontana divaricata leaves (IC50 of 12.73 µg/mL). Molecular docking of the 38 alkaloids, reported from the leaves of T. divaricata, into the active site of pancreatic lipase led to the identification of furan bridged bis-indole alkaloids viz., Conophylline (1), Conophyllinine (2) and Conophyllidine (3) as potential leads, while Taberhanine (4), a monomeric indole alkaloid was found to exhibit comparatively poor docking score. Further, molecular docking analysis of the top three molecules (1–3) highlighted the importance of hydrophobic interactions of the dimeric extension with the lid domain of pancreatic lipase, which was not found with 4. Molecular dynamics simulations of 1–4 in complex with pancreatic lipase, further confirmed the docking results, wherein compound 4 was comparatively less stable (RMSD ≈ 1.5 Å). Liquid chromatography–mass spectrometry analysis of the alkaloid-rich fraction of T. divaricata leaves indicated the presence of 1, while 2–4 were found to be absent. Molecule 1 was tested for pancreatic lipase inhibition potential, where it exhibited potent IC50 of 3.31 µM, comparable to that of orlistat (IC50 of 0.99 µM). Enzyme kinetic studies validated the in silico analyses, wherein compound 1 exhibited a competitive reversible inhibition of pancreatic lipase. The present study identified the bis-indole alkaloids of T. divaricata leaves as a new class of potent pancreatic lipase inhibitors.
Chromone Containing Hybrid Analogs: Synthesis and Applications in Medicinal Chemistry
(Wiley, 2023-06) Paul, Atish Tulshiram
The use of privileged scaffolds has proven beneficial for generating novel bioactive scaffolds in drug discovery program. Chromone is one such privileged scaffold that has been exploited for designing pharmacologically active analogs. The molecular hybridization technique combines the pharmacophoric features of two or more bioactive compounds to avail a better pharmacological activity in the resultant hybrid analogs. The current review summarizes the rationale and techniques involved in developing hybrid analogs of chromone, which show potential in fields of obesity, diabetes, cancer, Alzheimer's disease and microbial infections. Here the molecular hybrids of chromone with various pharmacologically active analogs or fragments (donepezil, tacrine, pyrimidines, azoles, furanchalcones, hydrazones, quinolines, etc.) are discussed with their structure-activity relationship against above-mentioned diseases. Detailed methodologies for the synthesis of corresponding hybrid analogs have also been described, with suitable synthetic schemes. The current review will shed light on various strategies utilized for the design of hybrid analogs in the field of drug discovery. The importance of hybrid analogs in various disease conditions is also illustrated.
Chromone-3-acrylic acid ester analogues: Design, synthesis and biological evaluation as potential pancreatic lipase inhibitors
(Elsevier, 2023-12) Paul, Atish Tulshiram
A novel series of 21 chromone-3-acrylic acid ester analogues (5aa-5cm) were designed, synthesized and evaluated for PL inhibitory activity. The molecular docking study indicate that all the designed chromone analogues have the good binding ability (MolDock score: -115.86 to -160.07 kcal/mol) in the active site of PL enzyme (PDB ID: 1LPB), showing interactions with essential amino acid residues (Phe77, Tyr114, Ser152, Phe215, Arg256). Also, all the analogues were checked for in silico drug likeness property and all were found to have drug like properties, obeying Lipinski rule of 5, with no PAINS alerts. Analogue 5am, with the best docking score, was stable in molecular dynamics simulation for 100 ns (maximum RMSD of 6.4 Å), showing crucial amino acid interactions for more than 60% of the simulation time. The structure of the synthesized analogues were then confirmed by NMR, HRMS and IR spectroscopy. Among the synthesized analogues, 5am and 5ad exhibited potent PL inhibition with IC50 of 5.16 ± 0.287 & 5.82 ± 0.933 µM, respectively, as compared with orlistat (IC50 = 0.86 ± 0.09 µM). The inhibition kinetics and in silico studies confirmed competitive type of inhibition of analogue 5am. The current work highlights the importance of chromone analogues as potential PL inhibitors. Further, the lead optimization may lead to much more potential PL inhibitors.
Computational insights into human UCP1 activators through molecular docking, MM-GBSA, and molecular dynamics simulation studies
(Elsevier, 2024-12) Paul, Atish Tulshiram
The prevalence of obesity is rapidly increasing worldwide. Brown adipose tissue activates uncoupling protein 1 (UCP1) to generate heat through bypassing ATP synthesis, offering a potential target for obesity treatment. Targeting UCP1 activation to induce thermogenesis through small molecules presents a promising approach for obesity management. In this study, molecular docking of UCP1 activators, using 2,4-dinitrophenol (DNP) as a reference ligand (PDB ID: 8J1N, docking score: −5.343 kcal/mol), identified seven top-scoring compounds: naringin (-7.284 kcal/mol), quercetin (-6.661 kcal/mol), salsalate (-6.017 kcal/mol), rhein (-5.798 kcal/mol), mirabegron (-5.535 kcal/mol), curcumin (-5.479 kcal/mol), and formoterol (-5.451 kcal/mol). Prime MM-GBSA calculation of the top-scored molecule (i.e., naringin) in the docking study showed ΔGBind of −70.48 kcal/mol. Key interactions of these top 7 activators with UCP1 binding pocket residues Trp280, Arg276, Glu190, Arg83, and Arg91 were observed. Molecular dynamics simulations performed for 100 ns confirmed complex stability, with RMSD values below 6 Å. Additionally, most activators showed favorable intestinal absorption (>90 %) and lipophilicity (LogP 2–4), with pKa values supporting their pharmacological potential as UCP1-targeting therapeutics for obesity. These findings provide a foundation for designing potent UCP1 activators by integrating docking scores, interaction profiles, statistical profiles from MD simulations, and physicochemical assessments to develop effective anti-obesity therapies.
Coumarin analogues as promising anti-obesity agents: in silico design, synthesis, and in vitro pancreatic lipase inhibitory activity
(Wiley, 2025-01) Paul, Atish Tulshiram
A set of coumarin-3-carboxamide analogues were designed, synthesized, and evaluated for their ability to impede pancreatic lipase (PL) activity. Out of all the analogues, 5dh and 5de demonstrated promising inhibitory activity against PL, as indicated by their respective IC50 values of 9.20 and 11.4 μM, as compared to Orlistat (IC50 = 0.97 μM). It was found that analogue 5dh inhibited PL in a competitive manner with an inhibition constant (Ki) of 4.504 μM. Additionally, the docking analysis validated the interactions between the analogue 5dh (MolDock score of −140.251 kcal/mol) and key amino acids in the active site, including Leu 153, Gly 76, Arg 256, His 151, Phe 77, and His 263. The inhibitory activity of these analogues was significantly correlated with their MolDock scores (Pearson's r = 0.6586). Finally, molecular dynamics simulation was also performed for 100 ns in order to elucidate the stability, confirmation and intermolecular interactions of the active analogue 5dh. The results of this investigation suggested that the complex maintained its stability despite the dynamic conditions exhibiting interactions with important amino acids. In summary, the outcomes indicated that the synthesized analogues exhibited the potential to inhibit PL activity.
Design and Synthesis of Echitamine-inspired Hybrid Analogues Containing Thiazolidinediones as Potential Pancreatic Lipase Inhibitors
(Bentham Science, 2022-11) Paul, Atish Tulshiram
Obesity is a multifactorial metabolic disease characterised by excessive accumulation of triglycerides. The prevalence and morbidity rates associated with obesity are increasing tremendously, posing a significant risk to society. Pancreatic lipase (PL) is a key enzyme responsible for the digestion of dietary triglycerides; hence its inhibition is considered an attractive target in obesity.
Design, synthesis and biological evaluation of N-substituted indole-thiazolidinedione analogues as potential pancreatic lipase inhibitors
(Wiley, 2021-04) Paul, Atish Tulshiram
Pancreatic Lipase (PL) is a key enzyme responsible for the digestion of 50%–70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole-TZD hybrid analogues were synthesized, characterized and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole-3-carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Analogues 6d and 6e exerted potent PL inhibitory activity (IC50-6.19 and 8.96 µM, respectively). Further, these analogues exerted a competitive mode of PL inhibition. Moreover, molecular modelling studies were in agreement with the in vitro results (Pearson's r = .8682, p < .05). The fluorescence spectroscopic analysis further supported the strong binding affinity of these analogues with PL. A molecular dynamics study (20 ns) indicated that these analogues were stable in a dynamic environment. Thus, the present study highlighted the potential role of indole-thiazolidinedione hybrid analogues as potential PL inhibitors and further optimization might result in the development of new PL inhibitory lead candidates.
Design, synthesis, biological evaluation and molecular modelling studies of conophylline inspired novel indolyl oxoacetamides as potent pancreatic lipase inhibitors
(RSC, 2020-06) Paul, Atish Tulshiram
A novel series of 21 indolyl oxoacetamide analogues was designed based on the natural product lead conophylline, and evaluated for their pancreatic lipase inhibitory activity using porcine pancreatic lipase (Type II). Analogues 12c and 12b exhibited comparatively greater potential (IC50 values of 2.95 and 3.26 μM) than conophylline (IC50 – 3.31 μM), while the standard drug, orlistat, exhibited a potent IC50 value of 0.99 μM. Further, analogues 12b and 12c exhibited reversible competitive inhibition similar to orlistat and conophylline, and possessed Ki values of 1.89 and 1.69 μM, respectively. Molecular docking of these analogues was in agreement with the in vitro results, wherein the MolDock scores exhibited significant correlation with their inhibitory activity. A 10 ns molecular dynamics simulation of 12c complexed with pancreatic lipase confirmed the role of extended alkyl interactions, along with π–π stacking and π–cation interactions, in stabilising the ligand in the active site (maximum observed RMSD ≈ 3.5 Å). ADMET prediction indicated the GI absorption of these analogues to be high; however, they did not possess carcinogenicity and hepatotoxicity in contrast to orlistat and conophylline.
Design, synthesis, biological evaluation and molecular modelling studies of indole glyoxylamides as a new class of potential pancreatic lipase inhibitors
(Elsevier, 2019-04) Paul, Atish Tulshiram
A series of eighteen indole glyoxylamide analogues were synthesized, characterized and evaluated for their pancreatic lipase inhibitory activity. Porcine pancreatic lipase (Type II) was used with 4-nitrophenyl butyrate (as substrate) for the in vitro assay. Compound 8f exhibited competitive inhibition against pancreatic lipase with IC50 value of 4.92 µM, comparable to that of the standard drug, orlistat (IC50 = 0.99 µM). Compounds 7a-i and 8a-i were subjected to molecular docking into the active site of human PL (PDB ID: 1LPB) wherein compound 8f possessed a potential MolDock score of −153.037 kcal/mol. Molecular dynamics simulation of 8f complexed with pancreatic lipase, confirmed the role of aromatic substitution in stabilizing the ligand through hydrophobic interactions (maximum observed RMSD = 3.5 Å).
Design, synthesis, biological evaluation and molecular modelling studies of novel diaryl substituted pyrazolyl thiazolidinediones as potent pancreatic lipase inhibitors
(Elsevier, 2017-08) Paul, Atish Tulshiram
A series of novel diaryl substituted pyrazolyl 2,4-thiazolidinediones were synthesized via reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinedione (TZD) and nitrobenzyl substituted 2,4-thiazolidinedione. The resulting compounds were screened in vitro for pancreatic lipase (PL) inhibitory activity. Two assay protocols were performed viz., methods A and B using p-nitrophenyl butyrate and tributyrin as substrates, respectively. Compound 11e exhibited potent PL inhibitory activity (IC50 = 4.81 µM and Xi50 = 10.01, respectively in method A and B), comparable to that of the standard drug, orlistat (IC50 = 0.99 µM and Xi50 = 3.72). Presence of nitrobenzyl group at N-3 position of TZD and nature of substituent at para position of phenyl ring at C-3 position of pyrazole ring notably affected the PL inhibitory activity of the tested compounds. Enzyme inhibition kinetics of 11e revealed its reversible competitive inhibition, similar to that of orlistat. Molecular docking studies validated the rationale of pharmacophoric design and are in accordance to the in vitro results. Compound 11e exhibited a potential MolDock score of −153.349 kcal/mol. Further, the diaryl pyrazolyl wing exhibited hydrophobic interactions with the amino acids of the hydrophobic lid domain. Moreover, the carbonyl group at 2nd position of the TZD ring existed adjacent to Ser 152 (≈3 Å) similar to that of orlistat. A 10 ns molecular dynamics simulation of 11e–PL complex revealed a stable binding conformation of 11e in the active site of PL (Maximum RMSD ≈ 3 Å). The present study identified novel thiazolidinedione based leads with promising PL inhibitory activity. Further development of the leads might result in potent PL inhibitors.
Design, synthesis, biological evaluation and molecular modelling studies of oxoacetamide warhead containing indole-quinazolinone based novel hybrid analogues as potential pancreatic lipase inhibitors
(RSC, 2022-05) Paul, Atish Tulshiram
A novel series of indolyl oxoacetamide-quinazolinone hybrid analogues (9aa–9df) were designed, synthesized, and evaluated for their in vitro pancreatic lipase (PL) inhibitory potential which may lead to efficient anti-obesity agents. All the synthesized hybrid analogues exhibited moderate to potent PL inhibitory activity (IC50 = 32.51 to 4.86 μM). Among all the analogues, 9ak, 9af, 9aj, and 9ah were found to have the most potent PL inhibitory activity (IC50 = 4.86, 5.73, 5.83, and 5.94 μM respectively), as compared to orlistat (IC50 = 0.86 μM). The most potent analogues 9af and 9ak were found to inhibit PL competitively with an inhibition constant (Ki) of 2.136, 1.648 μM. Furthermore, the docking study confirmed the binding of analogues 9ak and 9af (MolDock score of −161.25, −133.67 kcal mol−1) that exhibited docking interactions with important active site amino acids, namely Phe 77, Tyr 114, Ser 152, Arg 256, His 263, etc. Also, the analysis of analogue 9ak and 9af in SeeSAR revealed the covalent inhibition of PL. In molecular dynamics simulations of 100 ns, the complex between each analogue (9ak & 9af) and PL was found to be stable (RMSD < 1.5 Å). The present work highlights the importance of a hybrid drug design approach for the development of indole and quinazolinone containing hybrids as potential PL inhibitors.
Design, synthesis, biological evaluation, and molecular modeling studies of rhodanine derivatives as pancreatic lipase inhibitors
(Wiley, 2019-08) Paul, Atish Tulshiram
A series of rhodanine-3-acetic acid derivatives were synthesized via Knoevenagel condensation of rhodanine-3-acetic acid with various substituted aromatic aldehydes. The synthesized derivatives were screened in vitro for understanding the inhibitory potential towards pancreatic lipase (PL), a key enzyme responsible for the digestion of dietary fats. Derivative 8f exhibited a potential inhibitory activity towards PL (IC50 = 5.16 µM), comparable to that of the standard drug, orlistat (0.99 µM). An increase in the density of the aromatic ring resulted in potential PL inhibition. The enzyme kinetics of 8f exhibited a reversible competitive-type inhibition, similar to that of orlistat. Derivative 8f exhibited a MolDock score of -125.19 kcal/mol in docking studies, and the results were in accordance with their PL inhibitory potential. Furthermore, the reactive carbonyl group of 8f existed at a distance adjacent to Ser152 (≈3 Å) similar to that of orlistat. Molecular dynamics simulation (10 ns) of the 8f-PL complex revealed a stable binding conformation of 8f in the active site of PL (maximum root mean square displacement of ≈2.25 Å). The present study identified novel rhodanine-3-acetic acid derivatives with promising PL inhibitory potential, and further lead optimization might result in potent PL inhibitors.
Design, synthesis, evaluation, and molecular modeling studies of indolyl oxoacetamides as potential pancreatic lipase inhibitors
(Wiley, 2020-06) Paul, Atish Tulshiram
A series of indolyl oxoacetamide analogs was synthesized, characterized, and evaluated for their pancreatic lipase inhibitory activity using porcine pancreatic lipase (type II) and 4-nitrophenyl butyrate. Compound 8d exhibited a potent inhibition, with an IC50 value of 4.53 µM, followed by 8c (IC50 = 5.12 µM), compared with the standard drug, orlistat (IC50 = 0.99 µM). Furthermore, analogs 8c and 8d exhibited a reversible competitive inhibition, similar to orlistat. Molecular docking studies of the compounds 7a–f and 8a–f were in agreement with the in vitro results, wherein 8d exhibited a potential MolDock score of −163.052 kcal/mol. A 10-ns molecular dynamics simulation of 8d complexed with pancreatic lipase confirmed the role of π–π stacking and π–cation interactions with the lid domain and Arg 256, respectively, in stabilizing the ligand at the active site (maximum observed root mean square deviation ≈ 2 Å). The present study led to the identification of novel indolyl oxoacetamides (8a–d) as potential pancreatic lipase inhibitory leads that might further result in enhanced potency through lead optimization.
Design, synthesis, in silico molecular modelling studies and biological evaluation of novel indole-thiazolidinedione hybrid analogues as potential pancreatic lipase inhibitors
(RSC, 2021) Paul, Atish Tulshiram
Pancreatic lipase (PL) is a key enzyme responsible for the digestion of dietary triglycerides; hence its inhibition is considered as a promising target for the management and/or treatment of obesity. A new series of indole-thiazolidinedione (TZD) hybrid analogues were synthesized using a molecular hybridisation approach and evaluated for their anti-obesity effects via PL inhibition. The targeted analogues were synthesized via the condensation reaction between various substituted isatin with TZD in the presence of aqueous KOH in methanol. Amongst the synthesized analogues, 7k and 7m exhibited a potential PL inhibitory activity (IC50 – 7.30 and 9.51 μM, respectively). Kinetic study of these potent analogues revealed their competitive mode of enzyme inhibition. This fact was confirmed via fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking of the synthesized analogues was performed using human PL (PDB ID: 1LPB). The obtained MolDock scores were aligned with the in vitro PL inhibitory activity (Pearson's r = 0.9108, p < 0.05). Moreover, a stable conformation of the 1LPB-ligands suggested the stability of these complexes in the dynamic environment. These studies provided a basis for the potential role of the indole-TZD hybrids in PL inhibition and further optimization might result in the development of new lead candidates for obesity treatment.
Design, Synthesis, Molecular Modelling and in Vitro Evaluation of Indolyl Ketohydrazide-Hydrazone Analogs as Potential Pancreatic Lipase Inhibitors
(Wiley, 2023-08) Paul, Atish Tulshiram
Inhibition of Pancreatic lipase (PL) is considered to be a promising target for the management of obesity, owing to its crucial role in the digestion of dietary triglycerides. A series of 31 indolyl ketohydrazide-hydrazone analogs (5 aa–cm) were designed, synthesized and evaluated for their PL inhibitory potential. The analogs were designed using molecular modelling studies. The designed analogs were then synthesized by condensation of indolyl oxoacetohydrazide with various substituted benzaldehydes. All the synthesized analogs showed PL inhibitory activity in the range of 4.13–48.35 μM, as compared with orlistat (0.86±0.09 μM). The most potent analog 5 bi (IC50=4.13±0.95 μM) was found to show a competitive type of inhibition with Ki value of 0.725 μM. Additionally, the molecular docking study proved the binding of analog 5 bi at the active site of PL (PDB ID: 1LPB) with MolDock score of −141.279 kcal/mol. It also exhibited various interactions with the key amino acids namely Phe77, Phe215, Tyr114, Ser152, Arg256, His263, etc. Furthermore, the protein-ligand complex of analog 5 bi was found to be stable in molecular dynamics simulation for 100 ns with RMSD of less than 3.2 and 4 Å for the protein and ligand, respectively. The current work hereby provides a basis for the potential role of indolyl ketohydrazide-hydrazone analogs in PL inhibition and further optimization could result in the generation of new leads as anti-obesity agents.
Development and validation of a new HPTLC method for quantification of conophylline in Tabernaemontana divaricata samples obtained from different seasons and extraction techniques: Insights into variation of pancreatic lipase inhibitory activity
(Elsevier, 2018-01) Paul, Atish Tulshiram
Tabernaemontana divaricata (L.) R. Br. Ex Roem. & Schult Apocynaceae) is an important indole alkaloid rich Indian medicinal plant with conophylline being a potential lead in the treatment of diabetes mellitus and obesity. Seasonal variations and extraction techniques are two major variables that play a crucial role in the extractive yield of phytochemical constituents. Till date, there are no reports on quantification of conophylline from the leaves of T. divaricata of Indian origin, and its variation due to season and extraction techniques. The present study reports for the first time, development and validation of a new HPTLC method for the quantification of conophylline. A resolved peak of conophylline was achieved in the chromatogram with mobile phase of chloroform: methanol (90:10% v/v), when developed on a 15 cm length TLC plate. Further, the leaf samples of T. divaricata were collected during the months of August, November, February and May, and subjected individually to different extraction techniques viz., ultrasonic extraction, hot percolation and cold maceration. A total of 12 alkaloid rich fractions were obtained, and the extractive value of conophylline was found to be highest in August sample, when subjected to ultrasonic extraction (35.57 mg per 1 g of alkaloid rich fraction). Pancreatic lipase inhibitory activity of the alkaloid rich fractions was in correlation to their respective conophylline content (Pearson’s r = −0.7152) with potent activity exhibited by August sample, that was obtained by ultrasonic extraction (IC50 = 7.86 μg/mL).
Development and validation of a new HPTLC-HRMS method for the quantification of a potent pancreatic lipase inhibitory lead Echitamine from Alstonia scholaris
(Taylor & Francis, 2019-12) Paul, Atish Tulshiram
Alstonia scholaris is an important indole alkaloid rich medicinal plant with diverse pharmacological activity. To understand the effect of extraction techniques, the stem bark sample of A. scholaris was subjected to continuous hot percolation, ultrasonic extraction, and cold maceration techniques. Continuous hot percolation technique extractive exhibited a potential pancreatic lipase (PL) inhibitory activity and further bio-assay guided fractionation resulted in the isolation of echitamine with a PL inhibitory activity (IC50 = 10.92 µM). A new validated HPTLC-HRMS method was developed for the quantification of echitamine by using a mobile phase of chloroform: methanol (80:20, v/v) with 0.04% formic acid. Echitamine content in the individual extractives were in direct correlation with the PL inhibitory activity (Pearson’s r = −0.9409). The molecular docking studies further confirmed the PL inhibitory potential of echitamine. These results clearly highlight the role of echitamine as a natural product-based lead for potent PL inhibitory activity.