Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs

Hybrid bisindole-thiosemicarbazides analogs (1–18) were synthesized and screened for β-glucuronidase activity. All compounds showed varied degree of β-glucuronidase inhibitory potential when compared with standard d-saccharic acid 1,4-lactone (IC₅₀ = 48.4 ± 1.25 μM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional β-glucuronidase inhibition with IC₅₀ values ranging from 0.1 to 5.7 μM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC₅₀ values ranging from 7.12 to 15.0 μM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC₅₀ values 33.2 ± 0.75, 21.4 ± 0.30 and 28.12 ± 0.25 μM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds.     

Unsymmetrically disubstituted urea derivatives: A potent class of antiglycating agents

A series of unsymmetrically disubstituted urea derivatives 1–28 has been synthesized and screened for their antiglycation activity in vitro. Compounds 26 (IC₅₀ = 4.26 ± 0.25 μM), 1 (IC₅₀ = 5.8 ± 0.08 μM), 22 (IC₅₀ = 4.26 ± 0.25 μM), 6 (IC₅₀ = 6.4 ± 0.02 μM), 5 (IC₅₀ = 6.6 ± 0.26 μM), 2 (IC₅₀ = 7.02 ± 0.31 μM), 3 (IC₅₀ = 7.14 ± 0.84 μM), 27 (IC₅₀ = 7.27 ± 0.36 μM), 4 (IC₅₀ = 8.16 ± 1.04 μM), 21 (IC₅₀ = 8.4 ± 0.15 μM), 23 (IC₅₀ = 9.0 ± 0.35 μM) and 13 (IC₅₀ = 15.22 ± 6.7 μM) showed an excellent antiglycation activity far better than the standard (rutin, IC₅₀ = 41.9 ± 2.3 μM). This study thus provides a series of potential molecules for further studies of antiglycation agents.     

Terpenoids with cytotoxic activity from the branches and leaves of Pyrus pashia

Twenty terpenoids, including a new triterpenoid (1) and a new monoterpenoid (20), were isolated from the branches and leaves of Pyrus pashia. The structures of two new compounds were determined to be 2α, 3β, 27-trihydroxyolean-12-en-28-oic acid (1) and (4α)-3-(5,5-dimethyltetrahydrofuranyl)-1-buten-3-ol 3-O-β-d-glucopyranoside (20) on the basis of spectroscopic analysis (IR, HRESIMS, 1D and 2D NMR) and chemical method. Some of the isolated compounds were evaluated for their cytotoxic activity against a panel of human cancer cell lines by MTT assay, using cisplatin as a positive control. Compound 14 exhibited cytotoxic activities against A549 (IC₅₀ = 19.18 ± 4.26 μM), Hela (IC₅₀ = 12.56 ± 3.89 μM), SGC7901 (IC₅₀ = 10.48 ± 1.95 μM) and NHI-1975 (IC₅₀ = 7.38 ± 2.31 μM) cell lines as well as compound 12 displayed cytotoxic activities against A549 (IC₅₀ = 14.71 ± 1.47 μM) and Hela (IC₅₀ = 12.22 ± 1.88 μM) cell lines.     

Synthesis,in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase

A series of thiazole derivatives 1–21 were prepared, characterized by EI-MS and ¹H NMR and evaluated for α-glucosidase inhibitory potential. All twenty one derivatives showed good α-glucosidase inhibitory activity with IC₅₀ value ranging between 18.23 ± 0.03 and 424.41 ± 0.94 μM when compared with the standard acarbose (IC₅₀, 38.25 ± 0.12 μM). Compound (8) (IC₅₀, 18.23 ± 0.03 μM) and compound (7) (IC₅₀ = 36.75 ± 0.05 μM) exhibited outstanding inhibitory potential much better than the standard acarbose (IC₅₀, 38.25 ± 0.12 μM). All other analogs also showed good to moderate enzyme inhibition. Molecular docking studies were carried out in order to find the binding affinity of thiazole derivatives with enzyme. Studies showed these thiazole analogs as a new class of α-glucosidase inhibitors.     

Evaluation of bisindole as potent β-glucuronidase inhibitors: Synthesis and in silico based studies

Bisindole analogs 1–17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC₅₀ = 1.62 ± 0.04 μM), 6 (IC₅₀ = 1.86 ± 0.05 μM), 10 (IC₅₀ = 2.80 ± 0.29 μM), 9 (IC₅₀ = 3.10 ± 0.28 μM), 14 (IC₅₀ = 4.30 ± 0.08 μM), 2 (IC₅₀ = 18.40 ± 0.09 μM), 19 (IC₅₀ = 19.90 ± 1.05 μM), 4 (IC₅₀ = 20.90 ± 0.62 μM), 7 (IC₅₀ = 21.50 ± 0.77 μM), and 3 (IC₅₀ = 22.30 ± 0.02 μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC₅₀ = 48.40 ± 1.25 μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors.     

Synthesis of bis-Schiff bases of isatins and their antiglycation activity

Bis-Schiff bases 1–27 have been synthesized and their in vitro antiglycation potential has been evaluated. Compounds 21 (IC₅₀ = 243.95 ± 4.59 μM), 20 (IC₅₀ = 257.61 ± 5.63 μM), and 7 (IC₅₀ = 291.14 ± 2.53 μM) showed an excellent antiglycation activity better than the standard (rutin, IC₅₀ = 294.46 ± 1.50 μM). This study has identified a series of potential molecules as antiglycation agents. A structure–activity relationship has been studied, and all the compounds were characterized by spectroscopic techniques.     

Synthesis of 6-chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives: Antidiabetic,antioxidant, β-glucuronidase inhibiton and their molecular docking studies

6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1–26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and β-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC₅₀ = 240.10 ± 2.50 μM) and 4 (IC₅₀ = 240.30 ± 2.90 μM) was found to be most active compound of this series, while compounds 3 (IC₅₀ = 260.10 ± 2.50 μM), 6 (IC₅₀ = 290.60 ± 3.60 μM), 13 (IC₅₀ = 288.20 ± 3.00 μM) and 26 (IC₅₀ = 292.10 ± 3.20 μM) also showed better activities than the standard rutin (IC₅₀ = 294.50 ± 1.50 μM). In antioxidant assay, compound 1 (IC₅₀ = 69.45 ± 0.25 μM), 2 (IC₅₀ = 58.10 ± 2.50 μM), 3 (IC₅₀ = 74.25 ± 1.10 μM), and 4 (IC₅₀ = 72.50 ± 3.30 μM) showed good activities. In β-glucuronidase activity, compounds 3 (IC₅₀ = 29.25 ± 0.50 μM), compound 1 (IC₅₀ = 30.10 ± 0.60 μM) and compound 4 (IC₅₀ = 46.10 ± 1.10 μM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC₅₀ = 48.50 ± 1.25 μM) and their interaction with the enzyme was confirm by docking studies.     

Synthesis,in vitro α-glucosidase inhibitory activity and molecular docking studies of new thiazole derivatives

Current study based on the synthesis of new thiazole derivatives via “one pot” multicomponent reaction, evaluation of their in vitro α-glucosidase inhibitory activities, and in silico studies. All synthetic compounds were fully characterized by ¹H NMR, ¹³C NMR and EIMS. CHN analysis was also performed. These newly synthesized compounds showed activities in the range of IC₅₀ = 9.06 ± 0.10–82.50 ± 1.70 μM as compared to standard acarbose (IC₅₀ = 38.25 ± 0.12 μM). It is worth mentioning that most of the compounds such as 1 (IC₅₀ = 23.60 ± 0.39 μM), 2 (IC₅₀ = 22.70 ± 0.60 μM), 3 (IC₅₀ = 22.40 ± 0.32 μM), 4 (IC₅₀ = 26.5 ± 0.40 μM), 6 (IC₅₀ = 34.60 ± 0.60 μM), 7 (IC₅₀ = 26.20 ± 0.43 μM), 8 (IC₅₀ = 14.06 ± 0.18 μM), 9 (IC₅₀ = 17.60 ± 0.28 μM), 10 (IC₅₀ = 27.16 ± 0.41 μM), 11 (IC₅₀ = 19.16 ± 0.19 μM), 12 (IC₅₀ = 9.06 ± 0.10 μM), 13 (IC₅₀ = 12.80 ± 0.21 μM), 14 (IC₅₀ = 11.94 ± 0.18 μM), 15 (IC₅₀ = 16.90 ± 0.20 μM), 16 (IC₅₀ = 12.60 ± 0.14 μM), 17 (IC₅₀ = 16.30 ± 0.29 μM), and 18 (IC₅₀ = 32.60 ± 0.61 μM) exhibited potent inhibitory potential. Molecular docking study was performed in order to understand the molecular interactions between the molecule and enzyme. Newly identified α-glucosidase inhibitors except few were found to be completely non-toxic.     

Thymidine esters as substrate analogue inhibitors of angiogenic enzyme thymidine phosphorylase in vitro

Thymidine phosphorylase (TP) catalyzes the cleavage of thymidine into thymine and 2-deoxy-α-d-ribose-1-phosphate. Elevated activity of TP prevents apoptosis, and induces angiogenesis which ultimately leads to tumor growth and metastasis. Critical role of TP in cancer progression makes it a valid target in anti-cancer research. Discovery of small molecules as TP inhibitors is vigorously pursued in cancer therapy. In the present study, we functionalized thymidine as benzoyl ester to synthesize compounds 3–16. In vitro evaluation of thymidine esters for their thymidine phosphorylase inhibition activity was subsequently carried out. Compounds 4, 10, 14, and 15 showed good activities with lower IC₅₀ values than the standard, 7-deazaxanthine (IC₅₀ = 41.0 ± 1.63 μM). Among them, compound 14 showed five folds higher activity (IC₅₀ = 7.5 ± 0.8 μM), while 4 (IC₅₀ = 18.5 ± 1.0 μM) and 10 (IC₅₀ = 18.8 ± 1.2 μM) showed two folds higher activity than the standard. Compound 15 showed slightly better activity (IC₅₀ = 33.3 ± 1.5 μM) to the standard. Potent compounds were further subjected to kinetic and molecular docking studies to identify their mode of inhibition, and to study their interactions with the protein at atomic level, respectively. All active compounds were non-cytotoxic to mouse fibroblast 3T3 cell line. These results identify thymidine esters as substrate analogue (substrate-like) inhibitors of angiogenic enzyme thymidine phosphorylase for further studies.     

Dihydropyrimidones: As novel class of β-glucuronidase inhibitors

Dihydropyrimidones 1–37 were synthesized via a ‘one-pot’ three component reaction according to well-known Biginelli reaction by utilizing Cu(NO₃)₂·3H₂O as catalyst, and screened for their in vitro β-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC₅₀ = 28.16 ± .056 μM), 9 (IC₅₀ = 18.16 ± 0.41 μM), 10 (IC₅₀ = 22.14 ± 0.43 μM), 13 (IC₅₀ = 34.16 ± 0.65 μM), 14 (IC₅₀ = 17.60 ± 0.35 μM), 15 (IC₅₀ = 15.19 ± 0.30 μM), 16 (IC₅₀ = 27.16 ± 0.48 μM), 17 (IC₅₀ = 48.16 ± 1.06 μM), 22 (IC₅₀ = 40.16 ± 0.85 μM), 23 (IC₅₀ = 44.16 ± 0.86 μM), 24 (IC₅₀ = 47.16 ± 0.92 μM), 25 (IC₅₀ = 18.19 ± 0.34 μM), 26 (IC₅₀ = 33.14 ± 0.68 μM), 27 (IC₅₀ = 44.16 ± 0.94 μM), 28 (IC₅₀ = 24.16 ± 0.50 μM), 29 (IC₅₀ = 34.24 ± 0.47 μM), 31 (IC₅₀ = 14.11 ± 0.21 μM) and 32 (IC₅₀ = 9.38 ± 0.15 μM) found to be more potent than the standard d-saccharic acid 1,4-lactone (IC₅₀ = 48.4 ± 1.25 μM). Molecular docking study was conducted to establish the structure–activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as ¹H, ¹³C NMR, EIMS and HREI-MS.     

Synthesis of triazole Schiff bases: Novel inhibitors of nucleotide pyrophosphatase/phosphodiesterase-1

A series of Schiff base triazoles 1–25 was synthesized and evaluated for their nucleotide pyrophosphatase/phosphodiesterase-1 inhibitory activities. Among twenty-five compounds, three compounds 10 (IC₅₀ = 132.20 ± 2.89 μM), 13 (IC₅₀ = 152.83 ± 2.39 μM), and 22 (IC₅₀ = 251.0 ± 6.64 μM) were identified as potent inhibitors with superior activities than the standard EDTA (IC₅₀ = 277.69 ± 2.52 μM). The newly identified inhibitors may open a new avenue for the development of treatment of phosphodiesterase-I related disorders. These compounds were also evaluated for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase inhibitory potential and were found to be inactive. The compounds showed non-toxic effect towards PC3 cell lines.     

Triazinoindole analogs as potent inhibitors of α-glucosidase: Synthesis,biological evaluation and molecular docking studies

A new series of triazinoindole analogs 1–11 were synthesized, characterized by EI-MS and ¹H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC₅₀ value ranging between 2.46 ± 0.008 and 312.79 ± 0.06 μM when compared with the standard acarbose (IC₅₀, 38.25 ± 0.12 μM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC₅₀ values 2.46 ± 0.008, 37.78 ± 0.05, 28.91 ± 0.0, 38.12 ± 0.04, 37.43 ± 0.03, 36.89 ± 0.06 and 37.11 ± 0.05 μM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.     

Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases

To discover multifunctional agents for the treatment of Alzheimer’s disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC₅₀ values 4.12 ± 0.01, 8.12 ± 0.01 and 8.41 ± 0.06 μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC₅₀ = 0.85 ± 0.0001 μM). Three compounds 13, 24 and 3 having IC₅₀ values 6.51 ± 0.01, 9.22 ± 0.07 and 37.82 ± 0.14 μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC₅₀ = 0.04 ± 0.0001 μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.     

Design,synthesis and preliminary activity assay of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as novel Histone deacetylases (HDACs) inhibitors

Histone deacetylases (HDACs) are enzymes involved in tumor genesis and development. Herein, we report a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDACs inhibitors. The preliminary biological screening showed that most of our compounds exhibited potent inhibitory activity against HDACs. Within this series, five compounds, 13a (IC₅₀ = 0.58 ± 0.10 μM), 7d (IC₅₀ = 1.00 ± 0.16 μM), 8l (IC₅₀ = 1.06 ± 0.14 μM), 7i (IC₅₀ = 1.17 ± 0.19 μM) and 7a (IC₅₀ = 1.29 ± 0.15 μM) possessed better HDACs inhibitory activity than Vorinostat (IC₅₀ = 1.48 ± 0.20 μM). So these five compounds could be used as novel lead compounds for further design of HDACs inhibitors. The anti-proliferative activities of a few compounds and the structure–activity relationships are also briefly discussed.     

Coumarin sulfonates: As potential leads for ROS inhibition

Coumarin sulfonates 4–43 were synthesized by reacting 3-hydroxy coumarin 1, 4-hydroxy coumarin 2 and 6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC₅₀ = 54.2 ± 9.2 μM). Eleven compounds 6 (IC₅₀ = 46.60 ± 14.6 μM), 8 (IC₅₀ = 11.50 ± 6.5 μM), 15 (IC₅₀ = 21.40 ± 12.2 μM), 19 (IC₅₀ = 5.75 ± 0.86 μM), 22 (IC₅₀ = 10.27 ± 1.06 μM), 23 (IC₅₀ = 33.09 ± 5.61 μM), 24 (IC₅₀ = 4.93 ± 0.58 μM), 25 (IC₅₀ = 21.96 ± 14.74 μM), 29 (IC₅₀ = 12.47 ± 9.2 μM), 35 (IC₅₀ = 20.20 ± 13.4 μM) and 37 (IC₅₀ = 14.47 ± 5.02 μM) out of forty demonstrated their potential suppressive effect on production of reactive oxygen species (ROS) as compared to ibuprofen. All the synthetic derivatives 4–43 were characterized by different available spectroscopic techniques such as ¹H NMR, ¹³C NMR, EIMS and HRMS. CHN analysis was also performed.     

Design,synthesis and evaluation of novel metalloproteinase inhibitors based on l-tyrosine scaffold

A series of novel l-tyrosine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and histone deacetylase 8 (HDAC-8). The results showed that these l-tyrosine derivatives exhibited inhibitory profiles against MMP-2 and HDAC-8. The compounds 6h (IC₅₀ = 0.013 ± 0.001 μM) and 6j (IC₅₀ = 0.017 ± 0.001 μM) were equal potent MMP-2 inhibitors to the positive control NNGH (IC₅₀ = 0.014 ± 0.001 μM). As for HDAC-8 inhibition, some of the hydroxamate compounds, such as 6d (IC₅₀ = 3.6 ± 0.2 μM) and 6c (IC₅₀ = 5.8 ± 0.5 μM), were equal potent to the positive control SAHA (IC₅₀ = 1.6 ± 0.1 μM). Structure–activity relationships were also briefly discussed.     

Triterpenes from the roots of Lantana montevidensis with antiprotozoal activity

Bioassay guided fractionation of the roots of Lantana montevidensis (Verbenaceae) has resulted in the isolation and identification of three new triterpenoids; 13β-hydroxy-3-oxo-olean-11-en-28-oic acid (1), 12β,13β-dihydroxyolean-3-oxo-28-oic acid (2) and 12β,13β,22β-trihydroxyolean-3-oxo-28-oic acid (3) in addition to nine known compounds: oleanonic acid (4), oleanolic acid (5), 3β,25β-dihydroxy-olean-12-en-28-oic acid (6), lantadene A (7), 19α-hydroxy-3-oxo-olean-12-en-28-oic acid (8) pomolic acid (9), camaric acid (10) together with β-sitosterol (11) and β-sitosterol-3-O-β-d-glucoside (12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as HR-ESI–MS. The extracts and the isolated metabolites were evaluated for their antiprotozoal and antimicrobial activities. Compound 2 showed antibacterial activity against Staphylococcus aureus and methicillin resistant S. aureus with IC₅₀ values against both organisms of 2.1 μM and compound 10 showed activity against same organisms with IC₅₀ values 8.74 and 8.09 μM, respectively, compared to the positive control ciprofloxacin (IC₅₀ = 0.3 μM against S. aureus and MRSA). Compounds 1, 4, 5, 6, and 10 showed moderate antileishmanial activity with IC₅₀ values ranging between (2.54–14.95 μM) and IC₉₀ values ranging between (11.90–19.47 μM), using pentamidine as a control (IC₅₀ values 2.09 ≥ 16.8 μM) and IC₉₀ values ranging between (4.72 ≥ 16.8 μM). These compounds also showed highly potent antitrypanosomal activity with IC₅₀ values ranging between (0.39–7.12 μM) and IC₉₀ values ranging between (1.91–10.51 μM), which are more efficient than the DFMO, the antitrypanosomal drug employed as positive control (IC₅₀ and IC₉₀values 11.82 and 30.82 μM).     

5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes

On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC₅₀ = 8.15 ± 0.03–354.67 ± 0.19 μM) as compared to standard thiourea (IC₅₀ = 21.25 ± 0.15 μM). It is worth mentioning that derivatives 7 (IC₅₀ = 12.07 ± 0.05 μM), 8 (IC₅₀ = 10.57 ± 0.12 μM), 11 (IC₅₀ = 13.76 ± 0.02 μM), 14 (IC₅₀ = 15.70 ± 0.12 μM) and 22 (IC₅₀ = 8.15 ± 0.03 μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1–25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e. 2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.     

Schiff bases of 3-formylchromone as thymidine phosphorylase inhibitors

3-Formylchromone (1), 3-methyl-7-hydroxychromone (2) and Schiff bases of 3-formylchromone 3–19 have been synthesized and their anti-thymidine phosphorylase inhibitory activity was evaluated. Compounds 1–19 showed a varying degree of thymidine phosphorylase inhibition with IC₅₀ values 19.77 ± 3.25 to 480.21 ± 2.34 μM. Their activity was compared with the standard 7-deazaxanthine (IC₅₀ = 39.28 ± 0.76 μM). Compound 12 showed an excellent thymidine phosphorylase inhibitory activity with an IC₅₀ value of 19.77 ± 3.25 μM, better than the standard. Compound 4 also showed an excellent inhibitory activity (IC₅₀ = 40.29 ± 4.56 μM). The parent 3-formylchromone (1) and 3-methyl-7-hydroxychromone (2) were found to be inactive. The structures of the compounds were elucidated by using spectroscopic techniques, including ¹H NMR, EI MS, IR, UV and elemental analysis.     

Anticancer and α-chymotrypsin inhibiting diterpenes and triterpenes from Salvia leriifolia

Salvialeriol (1), a new abietane-type diterpene, was isolated from Salvia leriifolia Benth. (Salvia leriaefolia), along with two known abietane-type diterpenoids, 6-hydroxysalvinolone (2) and deacetylnemorone (3), and two known triterpenes, 2-acetoxylupeol (4), and lupine-2,3-diol (5). Compounds 2–5 are reported here for the first time from this species. Compound 4 was previously reported as a synthetic derivative of 5 and this is the first report of its isolation from a natural source. Compounds 2, 3 and 5 exhibited a potent antiproliferative activity against the prostate cancer cell lines (PC3) with IC₅₀ of 3.9 ± 0.1, 6.2 ± 0.1 and 2.8 ± 0.1 μM, respectively, and cervical cancer cell lines (HeLa) with IC₅₀ of 8.0 ± 0.3, 2.6 ± 0.1 and 2.7 ± 0.1 μM, respectively. Whereas compounds 1 and 4 showed moderate antiproliferative activities against the cell lines. Compounds 1–5 were also evaluated for the inhibition of α-chymotrypsin, a protease enzyme, and 2 exhibited a competitive inhibition of the enzyme (IC₅₀ = 188.8 μM).