Current Bioactive Compounds - Volume 16, Issue 5, 2020

Background: Boron is unusual to organic chemists, yet boron interacts greatly with organic biochemicals and has considerable bioactivity, especially as an antifungal and insecticide. The bestknown bioactive boron compounds are boric acid, its salt borax, and the closely related boronic acids. A newcomer is tavaborole (trade name Kerydin), recently developed and approved in 2014 for topical treatment of onychomycosis, a fungal infection of nails and the nail bed. It is timely to review the literature and explore the way in which these compounds may work. Methods: The focus of this review is to examine peer-reviewed literature relating to boric acid, boronic acid and tavaborole, the most bioactive boron-containing compounds, and the evidence for their proposed mechanism of antifungal action. In parallel with the literature, we have examined the fungistatic effects of boric acid on yeast. Results: All three compounds are reported to inhibit protein synthesis but their mechanism of action may differ. Chemistry studies indicate an interaction of boric acid with ribose and ribose-containing moieties such as NAD. In this review, we discuss the activity of boric acid and use both tavaborole and the boronic acids to exemplify the similar underlying mechanisms used. As there is a push to develop new antimicrobials, we demonstrate that boric acid’s fungistatic effect is alleviated with ribose, NAD and tryptophan. Conclusion: We speculate that boric acid inhibits yeast growth by disrupting tryptophan synthesis as well as downstream NAD, a rate limiting co-enzyme, essential for cellular function.

Background: Plants of the genus Inula are perennial herbs of the family Asteraceae. This genus includes more than 100 species, widely distributed throughout Europe, Africa and Asia including India. Many of them are indicated in traditional medicine, e.g., in Ayurveda. This review explores chemical constituents, medicinal uses and pharmacological actions of Inula species. Methods: Major databases and research and review articles retrieved through Scopus, Web of Science, and Medline were consulted to obtain information on the pharmacological activities of the genus Inula published from 1994 to 2017. Results: Inula species are used either alone or as an important ingredient of various formulations to cure dysfunctions of the cardiovascular system, respiratory system, urinary system, central nervous system and digestive system, and for the treatment of asthma, diabetes, cancers, skin disorders, hepatic disease, fungal and bacterial infections. A range of phytochemicals including alkaloids, essential and volatile oils, flavonoids, terpenes, and lactones has been isolated from herbs of the genus Inula, which might possibly explain traditional uses of these plants. Conclusion: The present review is focused on chemical constituents, medicinal uses and pharmacological actions of Inula species and provides valuable insight into its medicinal potential.

Background: The present research reported isolation, characterization of protopine from Hedyotis corymbosa and investigation of in-vivo hepatoprotective activity of protopine against simvastatin induced hepatotoxicity in experimental rodents. Methods: Protopine was isolated from H. coryambosa by column chromatography using chloroform: methanol: diethylamine (9:1:1) as the mobile phase and structural characterization was done by UV, FTIR, 1H-NMR and 13C-NMR and mass spectroscopy, followed by determination of in-vivo liver protective effect of protopine against simvastatin (20 mg/kg, p.o.), induced hepatotoxicity in experimental rodents. The liver protective activity was assessed by interpreting distinct biochemical parameters like SGOT, SGPT, cholesterol, urea, total bilirubin, total protein and albumin along with the haematological and histopathological studies. Results: The reports of spectroscopic techniques confirmed that the isolated compound is protopine, an isoquinoline alkaloid. The treatment with protopine significantly at (P<0.05-P<0.001) and dosedependently reversed simvastatin induced elevated level of SGOT, SGPT, cholesterol, urea, total bilirubin and restored the total protein and albumin level in rodents. Furthermore, protopine also signifies the blood parameters at a dose of 11 and 22 mg/kg and restored the defence mechanism of the body. The histological examination revealed that protopine at a dose of 22 mg/kg showed the regeneration of hepatocytes around central vein with near normal liver architecture. Conclusion: The results of the current study confirm the liver protective effect of protopine against simvastatin induced hepatotoxicity and therefore, scientifically support its traditional use.

Background: This study was aimed to evaluate the protective effects of n-butanol extract of Chrysanthemum fontanesii against oxidative stress induced by sodium Valproate (VPA) in the brain of female mice in comparison to Vitamin E (Vit E). Methods: Mice were divided into 5 groups and treated daily for 12 days. They received VPA (300 mg/kg i.p. injection), C. fontanesii butanolic extract (100 mg/kg), and Vit E (100 mg/kg). Glutathione Peroxidase Activity (GPx), Reduced Glutathione (GSH), and lipid peroxidation end products in the brain were measured. Results: Subacute treatment of mice with VPA resulted in a significant increase in oxidative damage. At a dose of 100 mg/kg, both C. fontanesii and Vit E significantly reduced VPA-induced oxidative stress by inhibiting lipid peroxidation, increasing brain GSH content, and restoring the activity of GPx. Conclusion: It may be concluded that the phytoconstituents present in the n-butanol extract of aerial parts of C. fontanesii are responsible for the ameliorative effect of brain antioxidant/oxidant status affected by VPA.

Background: Alyssum L. is a genus of herbaceous perennial or annual plants belonging to the Brassicaceae family. Little is known about biochemical properties of Alyssum species, specially endemics to Iran. In particular, the species were A. homolocarpum (Fisch. & C.A.Mey.) Boiss., A. lepidotum Boiss., A. maritimum (L.) Lam. (now syn. of Lobularia maritima (L.) Desv.) and A. simplex Rudolph. and eight accessions were studied. These diverse species accessions were collected in six different areas. Materials and Methods: In this work, the Total Phenolic Content (TPC), the Total Flavonoid Content (TFD), the Total Flavonol Content (TFL), the Carotenoid content (Car) and the Anthocyanin content (Ant) of the leaf methanolic extracts of four Alyssum L. species collected in Iran, were assessed. The antioxidant activity assay for every extract obtained from the eight accessions was also carried out according to three distinct methodologies including three different methods including: DPPH, Beta carotene/ linoleic acid and phosphomolibdate assays. Results: The highest TPC, TFD and TFL values were separately observed in two different accessions of A. lepidotum whereas the highest carotenoid content was observed in one accession of A. homolocarpum and the highest anthocyanin content was observed in A. maritimum. Different results were observed for different methodolies for antioxidant evaluations methods and some of them were found to have values, expressed in mg/mL, much lower with respect to the control. The least DPPH activity and the highest total antioxidant activity with phosphomolybdate assay was found in A. lepidotum. Conclusion: The preliminary phytochemical screening and the evaluation of their antioxidant activities were reported here for the first time for Iranian Alyssum species. The findings eventually recommends, the use of those accessions in the ethnopharmacological and nutraceutical fields.

Background: Calendula arvensis is an annual Mediterranean plant growing in Morocco between Rabat and Khemissat. C. arvensisis is known in folk medicine as an anti-inflammatory and antipyretic remedy. However, few reports have investigated its pharmacological properties. Methods: The objective of the present study was to determine chemical composition of C. arvensis flowers, and to investigate their antidiabetic activities by mean of digestive enzyme inhibition. The profile of phenolic compounds was established by HPLC-DAD-QTOF-MS analysis. While the antidiabetic activity was evaluated by the in vitro enzyme inhibition assays. Results: Phytochemical analysis revealed the presence of anthocyanins, flavonoids, tannins, and saponins as major elements. Whereas, alkaloids and terpenes were not detected in the plant samples. The chromatographic quantification identified 18 metabolites, with the caffeic acid as a major element. C. arvensis aqueous and methanolic extracts exhibited higher inhibitory potential against α-amylase, α- glucosidase and ß-galactosidase compared to the hexanic extract. Conclusion: The present study brings evidence to the hypoglycemic effect of C. arvensis flowers through enzyme inhibitory activities, and identifies the possible phenolic compounds associated with this activity.

Background: Paracetamol (p-aminophenol) and salicylates are nonsteroidal antiinflammatory drugs that are widely used in the general population. The adverse effects of both drugs continue to be a focus of the pharmaceutical industry in the development of new molecules that will increase treatment safety. In this context, we tested nine compounds derived from paracetamol and salicylates, synthesized in our laboratory, for their safety and ex vivo and in vivo anti-inflammatory activity. Methods: We analyzed the cytotoxicity of the compounds in ex vivo mice neutrophils, and their ability to inhibit the production of pro-inflammatory mediators (nitric oxide and interleukin-6) after stimulating with LPS. Next, in the selected molecules, we evaluated the anti-inflammatory effect on an in vivo inflammatory model of acute lung injury in mice. All nine compounds were also submitted to the cytotoxicity assay, like the original compounds. Results: None of the compounds showed cytotoxicity under the cells used. However, of the initial compounds, only five demonstrated anti-inflammatory effect, inhibiting Nitric Oxide (NO) and interleukin 6 (IL-6) production by neutrophils stimulated with Lipopolysaccharide (LPS). After this initial trial, four modified compounds were able to reduce leukocyte migration and fluid leakage in the bronchoalveolar lavage of mice. However, only the compound 5a1, derived from the esterification of gentisic acid, was able to significantly inhibit the levels of all pro-inflammatory cytokines and increase the levels of antiinflammatory cytokines evaluated. Conclusion: In conclusion, all compounds showed a good safety profile, and many of them had an antiinflammatory effect. However, the compound derived from gentisic acid is highlighted for its significant effects ex vivo and in vivo and in this context, we believe that this compound is a potential candidate for the development of a new anti-inflammatory drug.

Background: Vietnam currently imports up to 90% of the pharmaceuticals it consumes and 100% of the steroid-based pharmaceuticals. The ability for efficient chemical synthesis of the steroids could create commercial opportunities to address this issue. Synthesis of 21-acetoxypregna-1,4,9(11)- triene-17α,21-diol-3,20-dione is considered a key intermediate in the scheme of steroidal drug synthesis. Previous synthesis attempts of such steroids (corticoids) introduce a double bond at C-1(2) in the final stage of synthesis, which delivers a poor yield and reduces the economic efficiency of the process. Objective: To study and develop a novel and effective method for the synthesis of 21-acetoxypregna- 1,4,9(11)-triene-17α,21-diol-3,20-dione. Methods: Using 9α-hydroxyandrostenedione as a substrate chemical synthesis was performed as follows: pregnane side chain construction at C-17 (acetylene method), introduction of C-1(2) double bond (using SeO2), epimerization of C-17 (via 17-ONO2 ester) and Stork’s iodination. Results: 21-acetoxypregna-1,4,9(11)-triene-17α,21-diol-3,20-dione was prepared from 9α- hydroxyandrostenedione with an improved yield compared to previous attempts. Conclusion: Here, 21-acetoxypregna-1,4,9(11)-triene-17α,21-diol-3,20-dione has been synthesized from 9α-hydroxyandrostenedione based on a novel, effective and commercially feasible scheme. The introduction of the C-1(2) double bond at an earlier stage of the synthesis has increased the economic efficiency of the entire process. For the first time, the indirect epimerization mechanism has been clarified along with the configuration of the C-17 stereo-center which has been confirmed using NOESY data.

Background: The main aim of the study was to evaluate the bioactive properties of ethyl acetate crude extract of Streptomyces sp. VITASP with a view to assess their therapeutic potential. Methods: The morphological, physiological and the biochemical properties of the strain Streptomyces sp. VITASP were confirmed by conventional methods. The present study evaluated the antibacterial, antioxidant and cytotoxic activities. Results: The isolate was identified to be Streptomyces sp. (Genbank accession number: KR233807). The ethyl acetate extract of Streptomyces sp. VITASP showed maximum antibacterial activity of two Gram- positive and Gram- negative bacteria at 0.5mg/mL. The antioxidant potential of the crude extract exhibited strong reducing power activity at 0.5 mg/mL with 93±0.05% inhibition. The antiinflammatory and anti-diabetic properties were identified at 0.5 mg/mL concentration. The cytotoxic effect was found with an IC50 of 500μg/ mL on HeLa cell lines. The GC-MS analysis and the chromatogram patterns revealed major peak at 18.485 which corresponds to Pyrrolo[1,2-a]pyrazine-1,4-dione, Hexahydro-3-(2-methylpropyl. IR spectra showed the functional groups. HPLC Retention time of the peak was found to be 2.414 min. Conclusion: This work demonstrates that the extract should be considered as a useful source as an antioxidant and antimicrobial agent and gives further insight into the potential use of the compounds as drugs for various other bioactivities.

Background: The antioxidant activity and the total phenolic and flavonoid contents of the derived extracts (chloroform, ethyl acetate and n-butanol) of the 70% hydroalcoholic extract of the aerial parts of Centaurea solstitialis growing in Algeria was assessed. The active extracts were selected for phytochemical investigations. Methods: The antioxidant capabilities of the extracts were assessed using 1, 1-diphenyl-2- picrylhydrazyl radical (DPPH•) scavenging and Cupric Ion Reducing Antioxidant Capacity (CUPRAC) assays. Butylhydroxyanisole (BHA), butylhydroxytoluene (BHT) and α –tocopherol were used as positive controls. The total phenolic content and total flavonoid content of the extracts were determined as gallic acid equivalents and quercetin equivalents, respectively. Chromatographic methods were used to isolate the secondary metabolites and spectrometric and spectroscopic methods were used to determine their chemical structures. Results: The ethyl acetate extract exhibited the highest antioxidant activities followed by the n-butanol extract. The highest phenolic and flavonoid contents were found in the n-butanol extract. Phytochemical study of the ethyl acetate and n-butanol extracts led to the isolation of an undescribed guaianolide named 3-(4-hydroxybenzoyl)-cynaratriol and a known sesquiterpene lactone along with three known flavonoid glycosides. Their structures were established by spectral analyzes mainly high resolution electrospray ionisation mass spectrometry (HR-ESIMS) and 1D and 2D nuclear magnetic resonance experiments. Conclusion: The extracts of aerial parts of C. solstitialis showed significant antioxidant activities. An undescribed sesquiterpene lactone and four known secondary metabolites were isolated from the most active extracts.

Background: Rhus pentaphylla Desf. (Anacardiaceae) widely grown in Algeria, is an underutilized plant and remains poorly studied. To investigate for the first time, the chemical composition profile of essential oil and hydrosol extract; besides Total Phenolic (TPC), Flavonoid (TFC) and Condensed Tannins Contents (CTC) of fruits, leaves and roots, the fatty acid composition was assessed. The radical scavenging activity of R. pentaphylla extracts was then evaluated. Methods: Essential oil and hydrosol extract were isolated respectively by hydrodistillation and liquidliquid- extraction from the aerial parts of R. pentaphylla. The antioxidant activity was evaluated using 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) radical and ferric reducing antioxidant power (FRAP). Chemical compositions of various extracts were investigated using Gas Chromatography (GC) and GC-Mass Spectrometry (GC-MS). Results: The results of GC and GC-MS analysis revealed 83 components in essential oil and 75 components in hydrosol extract representing respectively 96.9% and 92.5% of the total extract composition. The main constituents were hexadecanoic acid (31.5%) followed by spathulenol (14.9%) in the oil while the higher amount present in the hydrosol extract was of spathulenol (14.2%). Otherwise, 13 and 18 fatty acids were identified in roots and fruits respectively. The highest levels of TPC and CTC were found in roots extracts while the highest quantity of TFC has been recorded in the leaves extract. Besides, hydrosol extract was able to scavenge DPPH and FRAP free radicals more efficiently than essential oil. Conclusion: R. pentaphylla contains bioactive substances that could be used as a new promising source of antioxidant compounds in different applications.

Background: Presentlytheeffectiveness of antifolate antimalarial drugs is decreasing due to the emergence of resistant Plasmodium strains. The aim of the present study was to determine the antimalarial effect of hybrid p-bromo phenyl thiazole-triazine derivatives against 3D7 strain of Plasmodium falciparum. Methods: Seventy-fivehybrid derivativeswere designed based on the lead molecule and docking was done against the active site of Pf-DHFR-TS (PDB i.d. 1J3i) with validated ligand fit protocol by using Discovery Studio 2.5. Based on the highest binding energy and the best docked pose, fifteen compounds were selected for the synthesis. Synthesized compounds were characterized by different spectroscopy methods and in-vitro antimalarial evaluation was done against the 3D7 strain of Plasmodium falciparum. Results: Fifteen compounds were synthesized by conventional and microwave assisted method and were characterized byFT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy. In-vitro antimalarial screening results showed that compounds ADG303, ADG 306 and ADG 302 have the highest activity against 3D7 strain of P. falciparum. Furthermore, docking result of these compounds having binding energies of -154.91, -165.981, -137.826 respectively showed similarity with reference compound WR99210 (-152.023) and also bound to Asp54 and Phe 58 amino acid at the active site of the receptor. Conclusion: The synthesized compound ADG303 exhibited an encouraging result which could be a new lead for antimalarial drug discovery.

Background: Ruta chalepensis is a shrub from the Mediterranean basin widely used in the traditional medicine. The plant presents an interesting composition containing alkaloids, coumarins and volatile oil. The present work aims to study the antibacterial and the cytotoxic effects of the ethanol extract, its fractions, and the alkaloid extract from the cultivated Ruta chalepensis. Methods: Extracts were tested against five bacterial strains using the agar well diffusion method and the broth micro-dilution technique for the determination of the Minimum Inhibitory Concentration (MIC). Brine shrimp assay was used to evaluate the cytotoxicity. Results: Chloroform fraction exhibited a strong antibacterial activity against S. aureus, and B. subtilis with inhibition diameters of 25.5±0.7 and 18.5±2.12mm at 50mg/ml and 100mg/ml, respectively. Butanol and aqueous fractions were found to be inactive against all the tested strains. Ethyl acetate was the only active fraction against E. coli. Alkaloids showed a strong growth inhibition of B. subtilis and S. aureus at low concentrations (22.5±0.71 and 18.00±0,00mm, respectively at 20mg/ml). The cytotoxicity evaluation using the brine shrimp larvae indicated a high effect of alkaloids with an LC50 of 27.51μg/ml supporting their antibacterial activity. Conclusion: These findings suggest a possible use of Ruta chalepensis as a source of antibacterial and anti-proliferative agents.

Background: Frozen yoghurt is a suitable vehicle to deliver bioactive compounds and beneficial microorganisms, and to develop new functional dairy products. Methods: Bifidobacterium bifidum was used in the manufacture of frozen yoghurt, whereas skim milk powder was substituted by Nanoparticles Coconut Flour (NCF) and Coconut Flour (CF). The physicochemical, microbiological and sensory properties were assessed for frozen yoghurt from different treatments. Results: The prepared NCF by ball-milling had sizes that range between 81.96nm to 83.53nm. The addition of NCF affected variably the pH values, moisture content, the overrun, fiber content, freezing points and viscosity of the prepared frozen yoghurt depending on the ratio of substituted skim milk. Also, the addition of NCF improved the viability of Bifidobacterium bifidum, Bifidobacterium breve, Streptococci, and Lactobacilli and total bacterial count of frozen yoghurt during frozen storage. The addition of NCF improved the sensory properties of frozen yoghurt. Conclusion: The use of Nanoparticles Coconut Flour (NCF) and Bifidobacterium sp., in the preparation of frozen yoghurt improved its physicochemical, microbiological and sensory properties.

Background: Valeriana jatamansi Jones (Syn. V. wallichii DC.; Fam. – Valerianaceae) is a medicinal plant species, endemic to the Himalayan regions of India and rich in presence of iridoids. This plant species possessed antimicrobial, antioxidant and anti-inflammatory properties. Methods: The shade-dried roots were powdered, percolated with 95% ethanol for 36 h at room temperature (3-times) and filtrate used for isolation of iridoids. The isolated compounds identified based on physical and spectral data analysis. For the enhancement of production of iridoids, the callus cultures established on Murashige and Skoog (MS) culture medium with variable concentrations of growth hormones. The isolated iridoids estimated by using High Performance Liquid Chromatography (HPLCSPD- M10A photodiode array detector) and Gas Chromatography–Mass Spectrometry (GC-MS) analysis. The anti-inflammatory activity of iridoids assessed by using carrageenan and Complete Freund's Adjuvant (CFA-induced adjuvant) models in experimental rats. The total eight bacterial and five fungal strains used for determination of antimicrobial activity. The activity assessed by using microdilution method. Results: Total seven iridoids were isolated from ethyl acetate fraction and their production estimated in cell cultures. The maximum accumulation (69.39±0.45 mg/g) of jatamanvaltrate S was observed in 2, 4- D (4.0 mg/l) and kinetin (1.0 mg/l) supplemented MS culture medium. Maximum anti-inflammatory activity demonstrated by jatamanvaltrate R (46.8%) at the dose of 20 mg/kg body weight (bw) at 8 h after carrageenan injection. Similarly, the jatamanvaltrate R also displayed maximum inhibitory activity (49.9%) to CFA-induced adjuvant arthritis in rats on day 8. The strongest antibacterial activity was exhibited by jatamanvaltrate S (21 μg/ml) against Staphylococcus aureus while maximum antifungal efficacy displayed by jatamanin B (30 μg/ml) against Penicillium chrysogenum. Conclusion: In this study, all the isolated iridoids found as bioactive molecules and exhibited promising anti-inflammatory and antimicrobial activities.

Background: Ashwagandha (Withania somnifera) is an important herb in the Indian traditional system of medicine for neurological disorders. However, the efforts for isolation and characterisation of a molecule with anti-depressant activity and development as a potent dosage form are limited. Objective: The objective of the present study was to characterize the Ashwagandha extract for its antidepressant fraction or constituent and to improve biological benefits at low doses. Methods: Aqueous methanol extract of Ashwagandha was prepared and fractionated into withanolides and flavonoids rich fractions. Withanolide rich fraction was subjected to phytochemical analysis to identify the active molecule/s. The compound was purified by using a semi-preparative HPLC system; identified using various spectroscopic techniques and anti-depressant activity was evaluated in rats. Enteric coating was performed on the extract and fractions after granulation and anti-depressant activity of coated samples were evaluated in rats. Results: Aqueous methanol extract of Ashwagandha and withanolide rich fraction showed prominent dose-dependent anti-depressant activity in forced swim test in rats. Phytochemical analysis of active fraction resulted in the isolation and characterization of a major withanolide glycoside present, namely withanoside X. Enteric coated aqueous methanol extract, withanolide rich fraction and withanoside X showed significant antidepressant activity at low doses as compared to the uncoated forms. Conclusion: The active fraction/isolated compound is sensitive to low pH of the stomach, thus enteric coating might be beneficial to protect the actives in the stomach, facilitating the sustainable release into the intestine and in turn reduce the dosage.

Background: Fenugreek seeds are employed in many traditional systems as an antibacterial, antidiabetic agent, gastric stimulant, and also for anti-invasive activity. Therefore, it is a suitable bioactive marker to establish the quality of crude drug and its formulations. Method: A rapid, simple and sensitive LC-MS/MS analytical method was developed and validated for the determination of trigonelline extracted from Trigonella foenum-graecum (L.) (Fenugreek) and marketed dietary supplements using Etofylline as an internal standard. The objective of the present study is to quantify Trigonelline extracted from Trigonella foenum graecum L. (fenugreek) and marketed dietary supplements. Chromatographic separation was achieved on a Zorbax C18 column (50mm x 4.6mm i.d, 5μ particle size). The samples were eluted using 0.1% Formic acid in water: Methanol (20:80%v/v) at a flow rate of 0.5ml/min with a runtime of 5 min. The eluents were monitored using a tandem mass spectrometer equipped with an electro spray ionization source in positive mode. Results: The analysis was performed in multiple reaction monitoring (MRM) mode by quantifying the ion transitions from m/z 138.0→92.5 (Trigonelline) and m/z 225.0→180.90 (IS). The developed method was linear over the concentration range 5-50 ng/mL. The LOD and LOQ were found to be 1.0 ng/mL and 10.0 ng/mL, respectively. The correlation coefficient (r2) was found to be ≥0.998 for Trigonelline. Conclusion: The proposed validated LC-MS/MS method offers a sensitive quantification of trigonelline in Trigonella foenum graecum L. (fenugreek) and marketed dietary supplements containing fenugreek seeds.

Background: The objective of the research was to examine the DPPIV inhibitor activity of synthetic derivatives of 2-aminobenzimidazole derivatives by the in-vivo method. Methods: Molecular docking was performed using homology model of receptors to identify the binding sites for the inhibitory activity of diabetes by means of- CDocker energy using the Discovery Studio (DS) 4.5 Novel 2-amino benzimidazole derivatives were synthesized from orthophenylene diamine with cyanogens bromide. The synthesized compounds were identified by IR,1HNMR,13CNMR, and MASS spectroscopic techniques. The products were analyzed for their DPPIV inhibitory effects on Wistar Albino rat. Results: The results revealed that benzimidazole with para-aminobenzoic acid possesses best DPPIV inhibitor activity. 2- amino benzimidazole incorporated with aromatic compounds were synthesized and assessed for their DPP-IV inhibitor activity. Conclusion: 2- amino benzimidazole with para-aminobenzoic acid can be used as a lead compound for the development of a new class of DPP-IV inhibitor.

Background: Launaea aspleniifolia Hook (Family Asteraceae) is used traditionally in medicine in Indian system for the treatment of leucoderma. This study was conducted to evaluate the hepatoprotective and antiulcer effects using the methanolic extract of Launaea aspleniifolia Hook (MELA). Methods: The MELA in the dose of 200 and 400 mg/kg body weight (b.w.) was administered orally, daily for 7 days to prevent the acetaminophen-induced hepatotoxicity and peptic ulcer. In order to determine the antioxidant enzymes activity, various enzymatic parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL), direct bilirubin (DBL), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), high density lipoproteins (HDL), random glucose test (RBS), serum creatinine levels (SCL) and direct bilirubin (DBL) were determined. Further, the histopathology of tissue and various gastric secretion parameters like free acidity, total acidity ulcer score, % ulcer inhibition, gastric volume, pH, Na+ and K+ and histopathology were determined in PLinduced ulcer model. Result: MELA showed dose-dependent hepatoprotective and ulcer protective effect in acetaminopheninduced hepatotoxicity and antiulcer activity. Furthermore, tissue antioxidant parameter such as reduced Malondialdehyde (MDA), histopathology was also investigated. MELA was more potent in controlling all the serological parameter of liver like ALT, AST, TBL, DBL, ALP, HDL, RBS, SCL, TP and ALB in a dose-dependent manner (P<0.05) induced by Acetaminophen. Apart from this, antiulcer activity MELA was confirmed by the low level of ulcer index along with the reduction of free acidity, total acidity ulcer score, % ulcer inhibition, gastric volume, Na+ and an increase K+, pH of gastric content in a dose-dependent manner (P<0.05) induced PL model. Conclusion: The results indicated a significant dose-dependent effect of MELA from injuries induced in liver and stomach. These protective effects of MELA can be examined in various other toxicities as alone and in combinations.