Biaryl carboxamide-based peptidomimetics analogs as potential pancreatic lipase inhibitors for treating obesity.

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.

Chromone Containing Hybrid Analogs: Synthesis and Applications in Medicinal Chemistry.

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.

Design, Synthesis, Molecular Modelling and in Vitro Evaluation of Indolyl Ketohydrazide-Hydrazone Analogs as Potential Pancreatic Lipase Inhibitors.

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 Šfor 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.

Topical Nanotherapeutics for Treating MRSA-Associated Skin and Soft Tissue Infection (SSTIs).

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) imposes a major challenge for the treatment of infectious diseases with existing antibiotics. MRSA associated with superficial skin and soft tissue infections (SSTIs) is one of them, affecting the skin's superficial layers, and it includes impetigo, folliculitis, cellulitis, furuncles, abscesses, surgical site infections, etc. The efficient care of superficial SSTIs caused by MRSA necessitates local administration of antibiotics, because oral antibiotics does not produce the required concentration at the local site. The topical administration of nanocarriers has been emerging in the area of drug delivery due to its advantages over conventional topical formulation. It enhances the solubility and permeation of the antibiotics into deeper layer of the skin. Apart from this, antibiotic resistance is something that needs to be combated on multiple fronts, and antibiotics encapsulated in nanocarriers help to do so by increasing the therapeutic efficacy in a number of different ways. The current review provides an overview of the resistance mechanism in S. aureus as well as various nanocarriers reported for the effective management of MRSA-associated superficial SSTIs.

Impact of quercetin on pharmacokinetics of quetiapine: insights from in-vivo studies in wistar rats.

Quercetin (QCN) is commonly used in high doses as a dietary supplement for weight loss. Psychotic patients are at greater risk of developing obesity than the general population. The present study was designed to understand the impact of QCN on the exposure of quetiapine (QTE), an anti-psychotic drug with narrow therapeutic index and brain penetrating capability. The content of QTE in rat plasma was analyzed through liquid chromatography-tandem mass spectrometry. The results showed a significant (p < 0.05) increase in exposure of QTE (peroral dosed) in the animals pre-treated with QCN as compared to the control group. All the animals pre-treated with QCN, succumbed to death within 3-5 min of intravenous dosing of QTE (1 mg/kg). The studies in rat liver S9 fraction indicated that QCN could increase the metabolic stability of QTE by inhibiting the activity of CYP enzymes. The brain to plasma ratio of QTE increased upon QCN pre-treatment (2.6 vs 7.7), which could be attributed to P-glycoprotein inhibition at the blood-brain barrier by QCN. The current set of studies indicated that serious herb-drug interaction between QCN and QTE might occur when they are co-administered. Caution is advised for concomitant use of QCN rich dietary supplements with QTE.

Rapid and cost-effective LC-MS/MS method for determination of hydroxycitric acid in plasma: Application in the determination of pharmacokinetics in commercial Garcinia preparations.

Garcinia cambogia is one of the most commonly used anti-obesity dietary supplements, and hydroxycitric acid (HCA) is a major constituent in the commercial preparations of Garcinia. High doses of HCA are often consumed without much awareness of its pharmacokinetic and toxicokinetic parameters, and therefore, a complete understanding of its effects is lacking. The first step in understanding these parameters is the availability of a reliable bioanalytical method. Here, we present the first report on a UPLC-MS/MS method for analysis of HCA in rat plasma after a simplified and cost-effective protein precipitation. Chromatographic separation of the analytes in the supernatant was achieved using hydrophilic interaction liquid chromatography, where mass parameters were optimized and a rapid 5-min quantitative assay was developed. The method was highly sensitive, accurate, precise and linear in the concentration range of 10.5-5000 ng/mL (validated according to the United States Food and Drug Administration guidelines). Further, the method was successfully used to describe the pharmacokinetic profile of HCA in rat plasma after the administration of pure HCA and commercial Garcinia preparations.

Design, synthesis, evaluation, and molecular modeling studies of indolyl oxoacetamides as potential pancreatic lipase inhibitors.

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.

Evaluation of biphenyl- and polychlorinated-biphenyl (PCB) degrading Rhodococcus sp. MAPN-1 on growth of Morus alba by pot study.

This study focused on isolation of bacteria with biphenyl/polychlorinated biphenyl (PCB) degrading ability from the rhizosphere of Morus alba (mulberry plant). Repetitive enrichment of rhizospheric soil samples with biphenyl resulted in the isolation of Rhodococcus sp. MAPN-1, identified by 16S rRNA gene sequence analysis. The bacterium showed growth on five different aromatic compounds (naphthalene, salicylic acid, benzoic acid, dibenzofuran and anthracene). Benzoic acid was detected as the major metabolite during biphenyl degradation using high-performance thin-layer chromatography (HPTLC) with Rf 0.42 at 254 nm. Further GC-MS/MS study showed 95% and 15% degradation of biphenyl and dichlorobiphenyl, respectively. A pot study was conducted to evaluate the effect of presence of biphenyl on M. alba and the role of biphenyl degrader Rhodococcus sp. MAPN-1 in relation to phytoremediation. Morus alba twigs in biphenyl spiked soil (100 mg/kg and 300 mg/kg) inoculated with Rhodococcus sp. MAPN-1 showed growth, whereas, growth of plants (control) was adversely affected in biphenyl-spiked uninoculated soil. It is the first report of isolation of Rhodococcus sp. MAPN-1 from the rhizosphere of Morus alba, its capability to degrade biphenyl, thereby showing a positive effect on the plant growth grown in biphenyl spiked soil.

Design, synthesis, biological evaluation and molecular modelling studies of indole glyoxylamides as a new class of potential pancreatic lipase inhibitors.

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 modeling studies of rhodanine derivatives as pancreatic lipase inhibitors.

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, biological evaluation and molecular modelling studies of novel diaryl substituted pyrazolyl thiazolidinediones as potent pancreatic lipase inhibitors.

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=4.81µM and Xi50=10.01, respectively in method A and B), comparable to that of the standard drug, orlistat (IC50=0.99µM 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 -153.349kcal/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 (≈3Å) similar to that of orlistat. A 10ns molecular dynamics simulation of 11e-PL complex revealed a stable binding conformation of 11e in the active site of PL (Maximum RMSD≈3Å). The present study identified novel thiazolidinedione based leads with promising PL inhibitory activity. Further development of the leads might result in potent PL inhibitors.

Synthesis, evaluation and molecular modelling studies of 2-(carbazol-3-yl)-2-oxoacetamide analogues as a new class of potential pancreatic lipase inhibitors.

A series of twenty four 2-(carbazol-3-yl)-2-oxoacetamide analogues were synthesized, characterized and evaluated for their pancreatic lipase (PL) inhibitory activity. Porcine PL was used against 4-nitrophenyl butyrate (method A) and tributyrin (methods B and C) as substrates during the PL inhibition assay. Compounds 7e, 7f and 7p exhibited potential PL inhibitory activity (IC50 values of 6.31, 8.72 and 9.58µM, respectively in method A; and Xi50 of 21.85, 21.94 and 26.2, respectively in method B). Further, inhibition kinetics of 7e, 7f and 7p against PL, using method A, revealed their competitive nature of inhibition. A comparison of the inhibition profiles of the top three compounds in methods B and C, provided a preliminary idea of covalent bonding of the compounds with Ser 152 of PL. Molecular docking studies of the compounds 7a-x into the active site of human PL (PDB ID: 1LPB) was in agreement with the in vitro results, and highlighted probable covalent bond formation with Ser 152 apart from hydrophobic interactions with the lid domain. Molecular dynamics simulation of 7e complexed with PL, further confirmed the role of aromatic groups in stabilising the ligand (RMSD ⩽4Å). The present study led to the identification of 2-(carbazol-3-yl)-2-oxoacetamide analogues 7a-x as a new class of potential PL inhibitors.

Pancreatic lipase and its related proteins: where are we now?

Obesity is a disease of epidemic proportions, with a worrisome upward trend. The high consumption of lipids, a major energy source, leads to obesity because of their high calorific value. Pancreatic lipase (PTL), produced by pancreatic acinar cells, hydrolyzes 50-70% of triacylglycerol (TAG) from food. PTL-related protein 1 (PLRP1) and 2 (PLRP2) are also produced by these cells. In vertebrates, PLRP1 has relatively less lipolytic activity, whereas PLRP2 has an essential role in lipid digestion, especially in infants. In this review, we summarize the structure and function of PTL, PLRP1, and PLRP2, and the metabolic fate of PTL inhibitors. We also discuss the current status of clinical trials on orlistat and its combinations for obesity treatment.

Long-term antitrypanosomal effect of quinapyramine sulphate-loaded oil-based nanosuspension in T. evansi-infected mouse model.

The goal of the present work consisted of the formulation development and evaluation of quinapyramine sulphate (QS)-loaded long-acting oil-based nanosuspension for improved antitrypanosomal effect. QS was transformed into a hydrophobic ionic complex using anionic sodium cholate (Na.C). The complex was characterized by FTIR, DSC, and XRD. Oil-based nanosuspension was prepared by dispersing the QS-Na.C complex in thixotropically thickened olive oil. The nanoformulation was found to be cytocompatible (82.5 ± 5.87% cell viability at the minimum effective concentration [MEC]) in THP-1 cell lines and selectively trypanotoxic (p < 0.0001). The pharmacokinetic studies of QS-Na.C complex-loaded oily nanosuspension showed 13.54-fold, 7.09-fold, 1.78-fold, and 17.35-fold increases in t1/2, AUC0-∞, Vz/F, and MRT0-ꝏ, respectively, as compared to free QS. Moreover, a 7.08-fold reduction in plasma clearance was observed after the treatment with the optimized formulation in Wistar rats. Furthermore, treatment with QS-Na.C complex-loaded oily nanosuspension (7.5 mg/kg) in T. evansi-infected mice model showed the absence of parasitaemia for more than 75 days after the treatment during in vivo efficacy studies. The efficacy of the treatment was assessed by observation of blood smear and PCR assay for DNA amplification. To conclude, our findings suggest that the efficient delivery of QS from the developed QS-Na.C complex-loaded oily nanosuspension could be a promising treatment option for veterinary infections against trypanosomiasis.

Recent innovations in topical delivery for management of rheumatoid arthritis: A focus on combination drug delivery.

Rheumatoid arthritis (RA) is an immune-mediated disease that necessitates a thorough understanding of its intricate pathophysiological mechanism for precise and effective therapeutic targeting. The European League Against Rheumatism (EULAR) has established guidelines for RA treatment, endorsing monotherapy or combination therapy with corticosteroids and synthetic disease-modifying antirheumatic drugs (sDMARDs). This review delves into clinical trials and research outcomes related to combination drug delivery, with an emphasis on the role of natural products in combination with synthetic drugs. Given the significant adverse effects associated with systemic administration, topical delivery has emerged as an alternative avenue for effective management of RA.

Discovery of thiazolidinedione-based pancreatic lipase inhibitors as anti-obesity agents: synthesis, in silico studies and pharmacological investigations.

A series of new 2,5-disubstituted arylidene derivatives of thiazolidinedione (16a-e, 17a-d, 18a-c) designed using molecular hybridization approach were synthesized, structurally characterized, and explored for their anti-obesity potential via inhibition of Pancreatic Lipase (PL). Compound 18a presented the most potent PL inhibitory activity with IC50 = 2.71 ± 0.31 µM, as compared to the standard drug, Orlistat (IC50 = 0.99 µM). Kinetic study revealed reversible competitive mode of enzyme inhibition by compound 18a with an inhibitory constant value of 1.19 µM. The most promising compound 18a revealed satisfactory binding mode within the active site of the target protein (human PL, PDB ID: 1LPB). Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analysis were performed for the most promising compound 18a, which showed potent inhibition according to the results of in vitro studies. Furthermore, a stable conformation of the 1LPB-ligand suggested the stability of this compound in the dynamic environment. The ADME and toxicity analysis of the compounds were examined using web-based online platforms. Results of in vivo studies confirmed the anti-obesity efficacy of compound 18a, wherein oral treatment with compound 18a (30 mg/kg) resulted in a significant reduction in the body weight, BMI, Lee index, feed intake (in Kcal), body fat depots and serum triglycerides. Compound 18a significantly decreased the levels of serum total cholesterol (TC) to 128.6 ± 0.59 mg/dl and serum total triglycerides (TG) to 95.73 ± 0.67 mg/dl as compared to the HFD control group. The present study identified disubstituted TZD derivatives as a new promising class of anti-obesity agents.Communicated by Ramaswamy H. Sarma.

UCP1 activation: Hottest target in the thermogenesis pathway to treat obesity using molecules of synthetic and natural origin.

Uncoupling protein 1 (UCP1) has been discovered as a possible target for obesity treatment because of its widespread distribution in the inner mitochondrial membrane of brown adipose tissue (BAT) and high energy expenditure capabilities to burn calories as heat. UCP1 is dormant and does not produce heat without activation as it is inhibited by purine nucleotides. However, activation of UCP1 via either direct interaction with the UCP1 protein, an increase in the expression of UCP1 genes or the physiological production of fatty acids can lead to a rise in the thermogenesis phenomenon. Hence, activation of UCP1 through small molecules of synthetic and natural origin can be considered as a promising strategy to mitigate obesity.

SET7, a lysine-specific methyl transferase: An intriguing epigenetic target to combat diabetic nephropathy.

Diabetic nephropathy (DN) is a dreadful complication of diabetes that affects ∼50% of diabetics and is a leading cause of end-stage renal disease (ESRD). Studies have linked aberrant expression of lysine methyltransferases (KMTs) to the onset and progression of DN. SET7 is a KMT that methylates specific lysine residues of the histone and nonhistone proteins. It plays an important role in the transforming growth factor-ß (TGF-ß)-induced upregulation of extracellular matrix (ECM)-associated genes that are responsible for the inflammatory cascade observed in DN. Inhibiting SET7 has potential to attenuate renal disorders in animal studies. This review will focus on the role of SET7 in DN and its potential as a therapeutic target to combat DN.

Molecular modelling, synthesis and in vitro evaluation of quinazolinone hybrid analogues as potential pancreatic lipase inhibitors.

Obesity is a multifactorial metabolic disorder, growing in an alarming rate across the world. Amongst the numerous targets explored for obesity management, inhibition of pancreatic lipase (PL) is considered as one of the promising approaches. Orlistat is the only PL inhibitory drug approved for long term treatment of obesity. However, it is reported to possess hepatotoxicity and nephrotoxicity. Thus, novel drug candidates that act through PL inhibition are considered the hour's need. Based on this aim, a series of quinazolinone hybrid analogues have been synthesized, characterized and evaluated for their PL inhibitory potential. The physicochemical properties and toxicity parameters suggested that these parameters are in an acceptable range for the screened analogues. Amongst the synthesised analogues, QH-25 exerted potential PL inhibition (IC50 = 16.99 ± 0.54 µM). Further, enzyme inhibition studies suggested a reversible competitive inhibition. Molecular docking of these analogues was in line with in vitro results, wherein the obtained MolDock scores exhibited a significant correlation with their inhibitory activity (Pearson's r = 0.6629). To further confirm the stability of the QH-25-PL complex in a dynamic environment, a molecular dynamics study (100 ns) was carried out and the results suggested that this complex is stable at dynamic conditions. Overall, these results shed light on the quinazolinone hybrids as potential PL inhibitors. Further structural modification may result in the development of potent anti-obesity agents which acts through PL inhibition.Communicated by Ramaswamy H. Sarma.

Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors.

A series of novel indole-thiazolidinedione hybrid analogues (7a to 7 u) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues, 7r was found to be the most active PL inhibitor with an IC50 of 2.67 µM. Furthermore, enzyme inhibition kinetics study revealed a competitive mode of inhibition by the analogues. This fact was confirmed via fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking was performed using human PL (PDB ID: 1LPB) and were in agreement with the in vitro results (Pearson's r = 0.8355, p < 0.05). A molecular dynamics study (100 ns) indicated that 7r was stable in a dynamic environment. The analogue 7r exhibited potential antioxidant activity and was devoid of cytotoxic effect on RAW 264.7 cells. Based on the in-vitro profiles, 7r was selected for the in-vivo pharmacological evaluation. Oral triglyceride tolerance test highlighted effect of 7r on the inhibition of triglyceride absorption. A four-week treatment of 7r in the HFD feed mice provided information regarding its anti-obesity effect with respect to parameters such as body weight, triglycerides, total cholesterol and high-density lipids. Quantification of the faecal triglyceride contents inveterates the potential role of 7r in the PL inhibition. Overall, the synthesized analogue 7r exerted an anti-obesity effect comparable to orlistat. All these results demonstrated the potential role of the newly synthesised indole-thiazolidinedione hybrid analogues in PL inhibition and may be studied further to find potential drug candidates for treating obesity.Communicated by Ramaswamy H. Sarma.