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TEN YEARS ON, THE KIMBERLEY PROCESS CERTIFICATION SCHEME AND ZIMBABWE’S MARANGE AND "CONFLICT DIAMONDS": LESSONS TO BE LEARNT N Shaik-Peremanov* SUMMARY Remove by editor - Prof Christa Rautenbach email: Christa.Rautenbach@nwu.ac.za

In this work, we designed and synthesized a novel, simple, low-cost, and effective chromone-based Schiff base ligand ( HL ) and its application as a chemosensor for Fe 3+ detection. The structure of the synthesized sensor bears carboxylic, azomethine, and carbonyl groups which act as chelating sites for the detection of Fe 3+ ions. The chemosensor HL exhibited highly selective detection of Fe 3+ via a significant colour change from yellow to brown. The colour change is due to the ligand-to-metal charge-transfer (LMCT) mechanism. The sensor ( HL ) was characterized using UV-Vis, FTIR, NMR ( 1 H- and 13 C), and mass spectroscopy. The ligand solubility, detection condition, and sensitivity assessment suggested optimal use of DMF-water (9:1 v/v) as a working solvent at pH 7.0. Among a list of 15 metal ions screened, HL was highly selective, with instant response, towards Fe 3+ ions without significant interferences with the other metal ions. The complexation ratio and association constants of HL was determined by Job's plot and Benesi-Hildebrand methods, and were 2:1 and 2.24 × 10 3+ was determined by Job's plot and Benesi-Hildebrand methods, and were 2:1 and 2.24 × 10 3 M -1 , respectively, with a detection limit of 2.86 μM. The HL probe was also applied to detect Fe 3+ in real samples with acceptable performance. The simple test strips have been successfully developed and applied to the visual monitoring of Fe 3+ ions with a detection limit of 68 µM. The DFT was used to examine the best interaction mode of HL with Fe metal to be Fe(III)-L or Fe(III)-2L. The chemical-reactivity and molecular electrostatic optional were figured to predict the interaction behaviour of the tested compounds.

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC 50 ) values ranging from 1.51 to 6.31 μM and anti-COX-2 activity with IC 50  = 0.29 μM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Andrographolide (AG), a major active constituent of Andrographis paniculata, is known to hinder proliferation of several types of cancer cells. However, its poor solubility and cellular permeability restrict its use in clinical applications. In this study, AG-loaded phytosomes (AG-PTMs) were formulated and optimized with respect to particle size using l-α-phosphatidylcholine (PC):AG ratio and sonication time (ST) as independent variables. The optimized formula was prepared at 1:2.7 for AG:PC molar ratio and 4.9 min for ST and exhibited a particle size of 243.7 ± 7.3 nm, polydispersity index (PDI) of 0.310 and entrapment efficiency of 72.20 ± 4.53. Also, the prepared formula showed a slow release of AG over 24-h period. The antiproliferative activity of AG-PTMs was investigated against the liver cancer cell line HepG2. AG-PTMs significantly repressed the growth of HepG2 cells with an IC 50 value of 4.02 ± 0.14 µM. AG uptake by HepG2 cells was significantly enhanced in incubations containing the optimized formula. AG-PTMs also caused G2-M cell cycle phase arrest and increased the fraction of apoptotic cells in pre-G1 phase. These effects were associated with induction of oxidative stress and mitochondrial dysfunction. In addition, AG-PTMs significantly upregulated mRNA expression of BAX and downregulated that of BCL2. Furthermore, AG-PTMs significantly enhanced the concentration of caspase-3 in comparison to raw AG. These data indicate that the phytosomal delivery of AG significantly inhibited HepG2 cell proliferation through enhanced cellular uptake, arresting cell cycle at the G2-M phase and inducing mitochondrial-dependent apoptosis.

Semisynthetic modifications of natural products have bestowed us with many anticancer drugs. In the present work, a natural product, eugenol, has been modified synthetically to generate new anticancer agents. The final compounds were structurally confirmed by NMR, IR, and mass techniques. From the cytotoxicity results, compound 17 bearing morpholine was found to be the most active cytotoxic agent with IC 50 1.71 (MCF-7), 1.84 (SKOV3), and 1.1 μM (PC-3) and a thymidylate synthase (TS) inhibitor with an IC 50 of 0.81 μM. Further cellular studies showed that compound 17 could induce apoptosis and arrest the cell cycle at the S phase in PC-3 carcinoma. The docking study strongly favors compound 17 to be a TS inhibitor as it displayed a similar interaction to 5-fluorouracil. The in silico pharmacokinetics and DFT computational studies support the results obtained from docking and biological evaluation and displayed favorable pharmacokinetic profile for a drug to be orally available. Compound 17 was found to be a promising TS inhibitor which could suppress DNA synthesis and consequently DNA damage in prostate cancer cells., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC 50 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC 50 0.39 μM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase.

Cancer and microbial infections constitute a major burden and leading cause of death globally. The development of therapeutic compounds from natural products is considered a cornerstone in drug discovery. Therefore, in the present study, the ethanolic extract and the fractions of Dodonaea viscosa and Juniperus procera were evaluated for anticancer and antimicrobial activities. It was found that two fractions, JM and DC, exhibited promising anticancer and antimicrobial activities. The JM and DC fractions were further modified into ZnO nanocomposites, which were characterized by SEM, XRD, TGA, and EDX. It was noted that the synthesized nanocomposites displayed remarkable enhancement in cytotoxicity as well as antibacterial activity. Nanocomposite DC-ZnO NRs exhibited cytotoxicity with IC 50 values of 16.4 ± 4 (HepG2) and 29.07 ± 2.7 μg/mL (HCT-116) and JM-ZnO NRs with IC 50 values of 12.2 ± 10.27 (HepG2) and 24.1 ± 3.0 μg/mL (HCT-116). In addition, nanocomposites of DC (i.e., DC-ZnO NRs) and JM (i.e., JM-ZnO NRs) displayed excellent antimicrobial activity against Staphylococcus aureus with MICs of 2.5 and 1.25 μg/mL, respectively. Moreover, these fractions and nanocomposites were tested for cytotoxicity against normal fibroblasts and were found to be non-toxic. GC-MS analysis of the active fractions were also carried out to discover the possible phytochemicals that are responsible for these activities.

Benzimidazole is a nitrogen-containing fused heterocycle which has been extensively explored in medicinal chemistry. Benzimidizole nucleus has been found to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, antiviral, antitubercular and antidiabetic. A number of benzimidazoles such as bendamustine, pantoprazole have been approved for the treatment of various illnesses, whereas galeterone and GSK461364 are in clinical trials. The present review article gives an overview of the different biological activities exhibited by the benzimidazole derivatives as well as different methods used for the synthesis of benzimidazole derivatives in the past ten years., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

New thiazolidine-2,4-dione hybrids were designed and synthesized as potential peroxisome proliferator-activated receptor (PPAR)-γ agonists and thymidylate synthase inhibitors. All the synthesized compounds follow Lipinski's and Veber's rules and possess the desired pharmacokinetics properties. The PPAR-γ transactivation results displayed that compounds 12 (78.9%) and 11 (73.4%) were the most active compounds and they increased PPAR-γ gene expression by 2.2- and 2.4-fold, respectively. Compounds 12, 11, and 8 showed promising cytotoxicity, with IC 50 values ranging from 1.4 to 4.5 μM against MCF-7 cells and from 1.8 to 8.4 μM against HCT-116 cells. Compounds 11 and 12 also inhibited thymidylate synthase with IC 50 values of 5.1 and 3.2 μM, respectively, confirming their mode of action as thymidylate synthase inhibitors. Finally, molecular docking studies supported the in vitro biological activity results., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

A library of novel naproxen based 1,3,4-oxadiazole derivatives ( 8 - 16 and 19 - 26 ) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-(( S )-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1 H -1,2,3-triazol-1-yl)phenol( 15 ) was the most potent compound against MCF-7 and HepG2cancer cells with IC 50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC 50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC 50 0.41 μM compared to standard drug Erlotinib (IC 50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives ( 6 - 18 ) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7 , 8 , 9 , 10 , and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1 H -1,2,3-triazol-1-yl)phenol ( 9 ) was the best compound against all three tested cell lines, MCF-7 (IC 50 1.1 μM), HCT-116 (IC 50 2.6 μM), and HepG2 (IC 50 1.4 μM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC 50 in the range 1.95-4.24 μM, whereas the standard drug, Pemetrexed, showed IC 50 7.26 μM. The antimicrobial results showed that some of the compounds ( 6 , 7 , 9 , 16 , and 17 ) exhibited good inhibition on Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential.

Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site. Subsequently, all the derivatives were primarily deduced for their antidiabetic potential by OGTT. The compounds that showed significant antidiabetic activity in OGT Test and also exhibited high dock scores were assessed further by in vitro PPAR transactivation assay to assure analogy between in vivo and in vitro studies. The antidiabetic activity of these active compounds was then evaluated on STZ induced diabetic model in vivo. The most active compounds were scrutinized for its effect on PPAR-γ gene expression and hepatotoxic effect. Finally, it was recapitulated that these derivatives can provide a new prospect towards the development of antidiabetic agents with fewer side effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Thymidylate synthase (TS) has been an attention-grabbing area of research for the treatment of cancers due to their role in DNA biosynthesis. In the present study, we have synthesised a library of thiazolidinedione-1,3,4-oxadiazole hybrids as TS inhibitors. All the synthesised hybrids followed Lipinski and Veber rules which indicated good drug likeness properties upon oral administration. Among the synthesised hybrids, compound 9 and 10 displayed 4.5 and 4.4 folds activity of 5-Fluorouracil, respectively against MCF-7 cell line whereas 3.1 and 2.5 folds cytotoxicity against HCT-116 cell line. Furthermore, compound 9 and 10 also inhibited TS enzyme with IC 50 = 1.67 and 2.21 µM, respectively. Finally, the docking studies of 9 and 10 were found to be consistent with in vitro TS results. From these studies, compound 9 and 10 has the potential to be developed as TS inhibitors.

Thymidylate synthase (TS) has emerged as a hot spot in cancer treatment, as it is directly involved in DNA synthesis. In the present article, nine hybrids containing 1,2,3-triazole and 1,3,4-oxadiazole moieties ( 6 - 14 ) were synthesized and evaluated for anticancer and in vitro thymidylate synthase activities. According to in silico pharmacokinetic studies, the synthesized hybrids exhibited good drug likeness properties and bioavailability. The cytotoxicity results indicated that compounds 12 and 13 exhibited remarkable inhibition on the tested Michigan Cancer Foundation (MCF-7) and Human colorectal Carcinoma (HCT-116) cell lines. Compound 12 showed four-fold inhibition to a standard drug, 5-fluoruracil, and comparable inhibition to tamoxifen, whereas compound 13 exerted five-fold activity of tamoxifen and 24-fold activity of 5-fluorouracil for MCF-7 cells. Compounds 12 and 13 inhibited thymidylate synthase enzyme, with an half maximal inhibitory concentration, IC 50 of 2.52 µM and 4.38 µM, while a standard drug, pemetrexed, showed IC 50 = 6.75 µM. The molecular docking data of compounds 12 and 13 were found to be in support of biological activities data. In conclusion, hybrids ( 12 and 13 ) may inhibit thymidylate synthase enzyme, which could play a significant role as a chemotherapeutic agent.

Callistemon lanceolatus (Sm.) Sweet grows all over the world and used to treat cough and bronchitis. The air-dried powder of the aerial parts was exhaustively extracted with methanol and the concentrated extract was adsorbed on silica gel for preparation of slurry. It was dried and subjected to silica gel column packed in petroleum ether. The column was eluted with organic solvents in order of increasing polarity to isolate 1-triacosanol ( 1 ), n -eicosanyl palmitate ( 2 ), n -heptadecanyl arachidate ( 3 ), n -tricosanyl palmitate, ( 4 ), 4-hydroxyphenethyl carbocerate ( 5 ), 4-hydroxyphenethyl gheddate ( 6 ), urs-12-en-3 α -acetoxy-18 β -H-28-oic acid ( 7 ) and stigmast-5-en-3 β -ol-3 β -D-glucuronopyranoside ( 8 ). Among them, compound 5 and 6 were new fatty acid ester isolated from this plant. Compound 7 showed MIC 32 µg/mL against E. coli which was comparable to amoxicillin having same MIC 32 µg/mL. Compound 5 and 6 showed significant antioxidant activity by inhibiting DPPH due to the presence of phenolic groups.

In the present work, a library of fifteen 2-hydroxy benzothiazole-linked 1,3,4 -oxadiazole derivatives have been synthesized and confirmed using different analytical techniques. All of the synthesized compounds have been tested for antibacterial and in silico pharmacokinetic studies for the first time. From the ADME predictions, compound 4 showed the highest in silico absorption percentage (86.77%), while most of the compounds showed more than 70% absorption. All of the compounds comply with the Lipinski rule of 5, suggesting that the compounds possess good drug likeness properties upon administration. Furthermore, all of the compounds follow the Veber rule, indicating good bioavailability and good intestinal absorption. The antibacterial results exhibited excellent to moderate activity. Compounds 5 , 9 , 12 , 14 , 15 , 16 , and 17 were the most active compounds against the tested bacterial strains. Compound 14 showed comparable MIC 6.25 ±0.2 μg/disc to the standard drug amoxicillin against the tested Gram-positive bacterial strains. Compounds 5 , 14 , 17 exhibited MIC 12.5 ±0.8 μg/disc, which was comparable to the standard drug against E. faecalis . It can be concluded that the synthesized compound could be used as a lead molecule in the development of new antibacterial agents with high efficacy., Competing Interests: CONFLICT OF INTEREST: The authors declare that they have no conflict of interest., (Copyright © 2020 The Author(s).)

A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF-α target. Among all the docked molecules, compound 3f showed best glide score of -6.89. All the synthesized compounds were evaluated for in vivo anti-inflammatory activity by carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory activity were further tested for their in vitro TNF α expression. Compounds 3b and 2b were found to show significant inhibition of 76.22% and 71.47%, respectively after 5 h in comparison with standard drug indomethacin, which showed 80.98% inhibition of inflammation. Compounds 3b and 2b also suppressed TNF α level by 65.03% and 60.90% as compared indomethacin, which showed 68.84% of inhibition. Compound 3b showed significant analgesic activity of 60.04%, and its activity was comparable with indomethacin (64.04%). Compounds 3b and 2b were also tested for their effect on protein expression of COX-2 and NF-κB in the liver tissues. Compounds 3b and 2b were further evaluated for their gastric risk and lipid peroxidation action and showed superior GI safety along with reduction of LPO as compared to indomethacin. Hepatotoxicity study showed that these two compounds did not cause any damage to liver., (© 2015 John Wiley & Sons A/S.)

A library of synthesized conjugates of phenoxy acetic acid and thiazolidinedione 5a-m showed potent peroxisome proliferator activated receptor-γ (PPAR-γ) transactivation as well as significant blood glucose lowering effect comparable to the standard drugs pioglitazone and rosiglitazone. Most of the compounds showed higher docking scores than the standard drug rosiglitazone in the molecular docking study. Compounds 5l and 5m exhibited PPAR-γ transactivation of 54.21 and 55.41%, respectively, in comparison to the standard drugs pioglitazone and rosiglitazone, which showed 65.94 and 82.21% activation, respectively. Compounds 5l and 5m significantly lowered the blood glucose level of STZ-induced diabetic rats. Compounds 5l and 5m lowered the AST, ALT, and ALP levels more than the standard drug pioglitazone. PPAR-γ gene expression was significantly increased by compound 5m (2.00-fold) in comparison to the standard drugs pioglitazone (1.5-fold) and rosiglitazone (1.0-fold). Compounds 5l and 5m did not cause any damage to the liver and could be considered as promising candidates for the development of new antidiabetic agents., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nineteen novel piperine based triazoles have been synthesized using click chemistry approach and were tested for in vivo anti-inflammatory activity. The most active compounds were evaluated for in vitro TNF-α expression. Compounds 3g and 3f were found to show significant in vivo inhibition of inflammation, 80.40% and 76.71%, respectively after 5 h in comparison to piperine (54.72%) and the standard drug indomethacin (77.02%) without causing any damage to the stomach. Compounds 3g and 3f suppressed TNF-α level by 73.73% and 70.64%, respectively and protein expression of COX-2, NF-κB and TNF-α more than indomethacin. Moreover, the compound 3g was found to show significant analgesic activity of 54.09% which was comparable with the indomethacin (57.43%)., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The present study aimed to investigate the anti-inflammatory activity of the ethanolic extract of the aerial parts of Trichosanthes dioica and its successive fractions. The effect on oxidative stress involved in the pathogenesis of inflammation was evaluated. The ethanolic extract and its successive fractions were administered at a dose of 150 and 300 mg/kg b. w. for testing their anti-inflammatory activity by a carrageenan-induced edema model. The results showed that the ethyl acetate fraction exhibited significant potency against inflammation. Pertaining to mechanistic insight, the anti-inflammatory effect might be attributed to the attenuation in tumor necrosis factor-α level (ELISA assay) and reduced expression of cyclooxygenase-2 and nuclear transcription factor-κB (immunohistochemistry). The alleviation in oxidative stress has been pertinent to the elevation in the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione) by active fractions. Furthermore, the ulcerogenic effect was insignificant even at a three times higher dose. Finally, it was concluded that the ethyl acetate fraction which showed significant biological potential against inflammation and oxidative stress could be viewed as a source of effective treatment., (Georg Thieme Verlag KG Stuttgart · New York.)

A library of novel 1,3,4-oxadiazole and 2-4-thiazolidinedione based bis-heterocycles 7 (a-r) has been synthesized which exhibited significant PPAR-γ transactivation and blood glucose lowering effect comparable with the standard drugs Pioglitazone and Rosiglitazone. Compounds 7m and 7r did not cause body weight gain and were found to be free from hepatotoxic and cardiotoxic side effects. Compounds 7m and 7r increased PPAR-γ gene expression by 2.10 and 2.00 folds, respectively in comparison to the standard drugs Pioglitazone (1.5 fold) and Rosiglitazone (1.0 fold). Therefore the compounds 7m and 7r may be considered as potential candidates for development of new antidiabetic agents., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

In the present study a library of twenty six benzenesulfonylureas containing thiophenylpyrazoline moiety has been synthesized. All the compounds were docked against PPAR-γ target. Most of the compounds displayed higher dock score than standard drugs, glibenclamide and rosiglitazone. All the synthesized compounds were primarily evaluated for their antidiabetic effect by oral glucose tolerance test. Further assessment of antidiabetic potential of sixteen active compounds was then done on STZ induced diabetic model. The results of in vivo activity by both the methods were found to be consistent with each other as well as with docking studies. Change in body weight of STZ induced animals post treatment was also assessed at the end of study. In vitro PPAR-γ transactivation assay was performed on active compounds in order to validate docking results and the most active compound 3 k was also shown to elevate gene expression of PPAR-γ. Furthermore, the compounds were screened by National Cancer Institute, Bethesda for anticancer effect and two compounds 3h and 3 i were selected at one dose level since they exhibited sensitivity towards tumor cell lines (mainly melanoma)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The present study aims at the synthesis of pyrazolines bearing benzothiazole and their evaluation as anti-inflammatory agents. The synthesized compounds were evaluated for their anti-inflammatory potential using carrageenan induced paw edema model. Two compounds 5a and 5d alleviated inflammation more than the standard drug celecoxib. Eight compounds 5 b, 5 c, 5 e, 5 g, 5 h, 6 b, 6 e and 6 f showed anti-inflammatory activity comparable to celecoxib. To understand the mode of action, COX-2 enzyme assay and TNF-α assay were carried out. All the active compounds were assessed for their cytotoxicity. The ulcerogenic risk evaluation was performed on the active compounds that were not found to be cytotoxic. Out of ten active compounds, two compounds (5 d and 6 f) were finally found to be the most potent anti-inflammatory agents attributing to the suppression of the COX-2 enzyme activity and TNF-α production without being either cytotoxic or ulcerogenic., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Traditionally, Aporosa lindleyana Baill. has been used against various ailments viz. jaundice, fever, headache, seminal loss and insanity. The present study aims to evaluate the anti-inflammatory and anti-oxidant activity of the ethanolic extract of Aporosa lindleyana Baill. bark and its fractions., Method: The anti-inflammatory activity of ethanolic extract of Aporosa lindleyana Baill. bark and its various fractions at doses of 200mg/kg and 300mg/kg b.w. has been carried out by a carrageenan induced hind paw edema method. To establish the probable mechanism of action, TNF-α and NO levels have been estimated by an ELISA method and the effect of active fraction on COX-2 and NF-κB expressions has been evaluated. The effect on the levels of anti-oxidative enzymes (CAT, SOD & GPX) by the ethanolic extract and its fractions has also been investigated. Furthermore, peptic ulcer and hepatotoxic risk evaluation has also been carried out at three times higher dose than that used in inflammatory in vivo model., Results: Among the extract and its various fractions tested for anti-inflammatory activity, the methanolic fraction at a dose of 300mg/kg showed significant inhibition in paw edema by 73% as compared to Indomethacin which showed 77% inhibition after 5h. The same dose of methanolic fraction also caused significant reduction in TNF-α (59.27%) and NO concentration (57.12%) while Indomethacin showed inhibition of 63.91% and 60.12%. The active methanolic fraction was also found to inhibit the expression of NF-κB and COX-2 induced by carrageenan. Histological studies showed that the ethanolic extract and its fractions did not cause any damage to the stomach as well as to liver. Moreover, the active fractions also decreased lipid peroxidation levels and increased the antioxidant enzyme activities (SOD, CAT, GPX)., Conclusion: The results of present study demonstrated that significant anti-inflammatory activity of methanolic fraction of Aporosa lindleyana may be attributed to the modulation of pro-inflammatory mediators. Same fraction was also found to be effective against oxidative stress as it was found to elevate the levels of anti-oxidative enzymes. It can therefore be concluded that the methanolic fraction could be explored as a disease modifying agent against inflammation and oxidative stress., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-γ transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-γ target in molecular docking study. PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A library of novel bis-heterocycles containing 2-mercaptobenzoxazole based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 4 exhibited the most potent in vivo anti-inflammatory activity with 66.66% and 61.11% inhibition in comparison to celecoxib which showed 72.22% and 65.55% inhibition after 3 h and 5 h respectively. The compounds 4 and 9 suppressed the COX-2 gene expression by 0.94 and 0.79 fold and exhibited a selective index (COX-1/COX-2) of 64.79 and 66.47 respectively in comparison to celecoxib (SI value of 75.56). The in silico molecular docking studies showed the interactions of these molecules with Tyr-59, Tyr-119 and Gly-121. When compared with the standard drug celecoxib, compounds 4, 5, 7, 9 and 16 did not cause any gastric ulceration., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Ethnopharmacological Relevance: Trapa natans L. has a folkloric reputation as nutrient, appetizer and astringent. Its utility as antidiabetic, anticancer, diuretic, aphrodisiac, antidiarrhoeal and in many other maladies is well reported in the literature. Therefore, the present study has been carried out to study the antihyperglycemic effect of root extract of Trapa natans L. and its various fractions. Furthermore, hepatotoxic effects and lipid peroxidation risks have also been evaluated., Methods: The ethanol extract and its successive fractions obtained from roots of Trapa natans have been administered in sucrose loaded and STZ- induced diabetic Wistar rats at doses of 50, 100 and 200mg/kg b.w. Glibenclamide was used as positive control. The evaluation of protective effects of extract as well as fractions against hepatotoxicity and lipid peroxidation at 600mg/kg b.w. has also been carried out., Results: The methanol fraction emerged as the most potent antihyperglycemic fraction. It has also been found that the ethanolic extract as well as its fractions did not cause any lipid peroxidation and hepatotoxicity risks., Conclusion: It can be concluded that the intense investigations of the methanol fraction obtained from Trapa natans root extract can be done to provide an alternative natural therapy for hyperglycemia., (© 2013 Published by Elsevier Ireland Ltd.)

A library of novel bis-heterocycles containing benzoxazolinone based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 3f exhibited potent selective COX-2 inhibition of 59.48% in comparison to standard drug celecoxib (66.36% inhibition). The compound 3i showed significant (p < 0.001, 50.95%), TNF-α inhibitory activity as compared to indomethacin (p < 0.001, 64.01%). The results of the carrageenan induced hind paw oedema showed that compounds 3a, 3f, 3i, 3o, and 3e exhibited potent anti-inflammatory activity in comparison to Indomethacin. The molecular docking studies revealed that 3i exhibits strong inhibitory effect due to the extra stability of the complex because of an extra π-π bond. The histopathology report showed that none of the compounds caused gastric ulceration., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Two new triterpenoids characterised as 30-normethyl fernen-22-one (capillirone, 1) and hopan-3β-ol (capillirol B, 2), along with two known triterpenoids, 4-α-hydroxyfilican-3-one and 3-β,4-α-dihydroxyfilicane, have been isolated from the ethanolic extract of the fronds of Adiantum capillus-veneris Linn. (Adiantaceae). Compounds 1 and 3 showed significant anti-inflammatory activity with 33.07% (p < 0.01) and 42.30% (p < 0.001) inhibition as compared to indomethacin that exhibited 60.00% (p < 0.001) inhibition after 3 h in the carrageenan-induced hind paw oedema method. Compound 3 showed potent anti-nociceptive activity with 42.37% inhibition as compared to indomethacin that showed 45.34% inhibition in the writhing test.

Phytochemical investigation of the aerial parts of Callistemon lanceolatus DC (Myrtaceae) led to the isolation of two new flavones characterized as 5,7-dihydroxy-6,8-dimethyl- 4' -methoxy flavone (1) and 8-(2-hydroxypropan-2-yl)-5-hydroxy-7-methoxy-6-methyl-4'-methoxy flavone (2) along with the seven known phytoconstituents. The structures of new compounds have been established on the basis of chemical and spectral studies and known compounds were compared with the published literature data. The isolated flavones exhibited blood glucose lowering effect in streptozotocin induced diabetic rats., (Copyright © 2012 Elsevier B.V. All rights reserved.)