Current Bioactive Compounds - Volume 15, Issue 6, 2019

Background: Currently, ringworm treatment drugs include two major categories: first, propylene amine drugs, such as terbinafine, butenafine and naftifine, which exert their bactericidal effects through inhibiting squalene cyclase, causing the lack of ergosterol and accumulation of squalene. The second category of imidazole drugs includes miconazole, econazole, clotrimazole, ketoconazole and bifonazole. Mechanism: These synthetic antifungal agents exhibits their action by inhibiting the lanosterol 14α- demethylation activity of fungal cell, leading to the prevention of the ergosterol synthesis of cell membrane, changing the cell membrane permeability, and resulting in the loss of important intracellular fungal material and causing fungal death. Applications: At present, Imidazole antifungal agents are commonly used drugs in clinical treatment of ringworm with extensive clinical applications. Conclusion: The present review covers the chemistry and detailed pharmacology aspects of luliconazole.

Background: Aromatic amino acid-based surfactants have been found to have interesting biological properties such as antibacterial and hemolytic activities. Recently, we have reported the antibacterial activity of a range of ester hydrochloride surfactants derived from L-Phenylalanine and LTyrosine. This study aims at assessing the antioxidant, α-glycosidase inhibitory and cytotoxic activities of a series of L-Phenylalanine and L-Tyrosine ester hydrochlorides. Molecular docking and BSA binding studies were also carried out in order to investigate their potential therapeutic targets. Methods: L-Phenylalanine and L-Tyrosine surfactants were tested as potential lipophilic antioxidants using the DPPH and ABTS assays. These surfactants were also tested for their α-glycosidase inhibitory activity using 4-nitrophenyl α -D-glucopyranoside (pNPG) as substrate. Their cytotoxicity effects were screened using HeLa and KB cell lines. Glide version 5.7 as implemented in Schrödinger suite 2013-1, was used for performing docking studies of L-Phenylalanine and L-Tyrosine dodecyl esters. The interaction of the ester hydrochlorides of L-Phenylalanine and L-Tyrosine with bovine serum albumin (BSA) was investigated using fluorometric titration. Results: The presence of the phenolic moiety in L-Tyrosine-based surfactants was found to enhance the antioxidant and α-glucosidase inhibitory activities compared to the L-Phenylalanine derivatives. The α- glucosidase and anticancer activities of the phenylalanine surfactants were found to increase with chain length up to C12 above which the activities exhibited a downward trend. In the case of the tyrosine series, an increase in chain length from C8 to C14 was found to decrease the α-glucosidase inhibitory activity and increase the anticancer activity of the surfactants. Binding studies with bovine serum albumin showed that the tyrosine surfactants displayed greater affinity for the serum albumin, owing to the presence of the phenolic group which altered the orientation of the surfactant molecule within the hydrophobic core of BSA. Conclusion: L-Tyrosine esters having a phenolic moiety were found to possess enhanced biological activity in terms of both the antioxidant and antidiabetic activities as well as also bind more strongly to Bovine serum albumin. Molecular docking studies of the phenylalanine and tyrosine surfactants of similar chain length with target proteins showed direct correlation with their anticancer and antidiabetic activity. Therefore, the findings show that these aromatic based surfactants derived from L-Tyrosine can act as promising antioxidant, antidiabetic and anticancer agents, and they can also be efficiently transported and eliminated in the body, making them useful candidates for drug designs.

Background: Herbal foods possess significant amounts of essential bioactive nutrients and offer clinical and therapeutic benefits. The aim of present research was to compare the antioxidant potential of black cumin extracts obtained using different extraction modes. Materials and Methods: Three solvents (methanol, acetone and hexane) were employed at different time intervals and ratios. However, Supercritical Fluid Extracts (SFE) were obtained at varying pressures (5500, 6500 and 7500 psi). Results: Outcomes revealed that total phenolics were maximum in methanolic extract (790.79±31.67 mg GAE/100 g) at 50 min. Similarly, DPPH and FRAP activity of methanolic extract was also better than other extracts as 80.99±4.02% and 27.44±0.88 mg TE/g, respectively. HPLC quantification exhibited that highest recovery of major bioactive component (thymoquinone) was obtained via supercritical extraction (12.38 mg/g) at 7500 psi. Conclusions: It is concluded that Pakistani variety of black cumin possess appreciable antioxidant activity which directly depends upon the extraction conditions. Among conventional solvents, methanol was evidenced to be more efficient. However, supercritical fluid extracts have proved a reliable mean for the extraction of thymoquinone.

Background: Resistance to malarial drugs represents a major obstacle in the treatment of disease, thereby increasing the need for more efficient drugs. The development of metal complexes offers the medicinal chemist an opportunity to expand the activity of drugs. For providing supportive therapy to the host to boost its immune system several new antimalarial drugs are being beneath research, but sufficient information on their efficacy is yet not available. Methods: In view of above, eight drug metal complexes (Ba (II), Ca (II), Zn (II), St (II), Hg (II), Fe (III), Cu (II), Ni (II) of Sulfamethoxazole (SMX) and Primaquine were synthesized and in-vitro evaluated for their antimalarial activity against malaria parasite Plasmodium falciparum by using fluorescence based assay. Result: The antimalarial activity of Nickel (EC50= 1.41μM) and Zinc (EC50=0.96μM) complexes have shown tremendous activity as compared to the standard drug Primaquine (EC50=0.07μM). The structures of all these newly synthesized derivatives were confirmed by spectral data (IR, 1H NMR, 13C NMR and Mass spectrometry). Conclusion: In conclusion, this study describes that the preparation and antimalarial evaluation of metal complexes of primaquine and sulphamethoxazole. Evaluation of their possible biological activities such as antimalarial activity was carried out and most of the synthesized compounds (Nickel and Zinc metal complexes) showed the good activity as compared to the standard drug primaquine. Therefore the compounds are appropriate candidates for more investigation and some more derivatives can be synthesized to get an imminent into the structure activity relationship of these compounds to be employed as biologically useful agents.

Background: Açaí (Euterpe oleracea), a “superfruit” consumed worldwide, is a Brazilian Amazon native fruit, with high nutritive value due to its high content of lipids, proteins, and fibers, besides bioactive compounds, such as anthocyanins, carotenoids and phenolic compounds in its composition associated with biological action beneficial to health. The increased consumption of this fruit has stimulated breeding programs in the search of plants and fruits with higher productivity and bioactive compounds, generating information for the development of new cultivars with improved attributes. This work aimed to study six different genotypes of açaí, developed by the breeding program, evaluating their physicochemical characteristics and proximate composition, bioactive compounds and antioxidant activity. Methods: The genotypes were analyzed for titratable acidity, pH, total soluble solids and proximate composition, such as moisture, protein, lipids, total fiber, carbohydrates and ashes contents. A spectrophotometric method using Folin-Ciocalteau reagent performed the phenolic compounds analysis and HPLC evaluated carotenoids and anthocyanins extracted exhaustively. The ABTS assay evaluated the antioxidant activity. Results: The L06P13 and L09P09 genotype presented higher content of total fiber, carbohydrates, and ashes when compared to the commercial sample used as a standard. Furthermore, L22P13 genotype showed the highest content of total anthocyanins (6745.81 mg/100g), total carotenoids (118 μg/g) and antioxidant activity (674.83 μM Trolox/g) when compared to commercial sample. Conclusion: The results revealed promising açaí genotypes and support the importance of advances in the area of functional foods and breeding programs.

Background: Since the Monastrol discovery in 1999 as the first inhibitor of Eg5, functionalized dihydropyrimidinones/thiones (DHPMs) have emerged as prototypes for drug design in different targets. The present work aimed to evaluate the antifungal activity of a chemical library of DHPMs. Methods: The compounds were obtained employing Biginelli reaction. Their antifungal activities were assessed against C. neoformans and C. albicans. Results: The compounds 1-i and 1-k inhibited moderately the fungal growth of C. neoformans, with compound 2-k presenting MIC80 values of 62.5-125 μg·mL-1. Considering activity against C. albicans, the compounds 1-i and 1-n present an MIC50 value of 125-250 μg·mL-1. Conclusion: The changes performed in DHPM scaffold appear to be valuable for generating compounds with potential antifungal effect.

Background: Tuberculosis is a contagious, air borne disease and second leading cause of death among infectious diseases worldwide. Fluoroquinolones are well-known antibacterial agents and they were recommended as second-line of antitubercular drugs. Method: A series of novel fluoroquinolone analogs 6-24 was effectively synthesized. An attempt was made by tagging the substituted pyrazole on to fluoroquinolones for the first time at C-7 position. The newly synthesized compounds were characterized by FTIR, 1HNMR, ESI-MS, HR-MS and elemental analysis. The in vitro antibacterial activity of all the title compounds was investigated against various gram positive, gram negative bacterial organisms and in vitro antitubercular activity against Mycobacterium Tuberculosis H37Rv strain. Result: Most of the synthesized compounds showed comparable activity against the entire gram positive and gram negative bacterial organisms. Fluoroquinolone 16 showed enhanced activity against both type of bacterial strains and compound 11showed promising activity against MTB-H37Rv strain. Conclusion: Some of the novel fluoroquinolone analogs (11, 16) showed potent antibacterial, antitubercular activity.

Background: [1, 3, 4]oxadiazolenone core containing chalcones and nucleosides were synthesized by Claisen-Schmidt condensation of a variety of benzaldehyde derivatives, obtained from oxidation of substituted 5-(3/6 substituted-4-Methylphenyl)-1, 3, 4-oxadiazole-2(3H)-one and various substituted acetophenone. The resultant chalcones were coupled with penta-O-acetylglucopyranose followed by deacetylation to get [1, 3, 4] oxadiazolenone core containing chalcones and nucleosides. Various analytical techniques viz IR, NMR, LC-MS and elemental analysis were used to confirm the structure of the synthesised compounds.The compounds were targeted against Bacillus subtilis, Staphylococcus aureus and Escherichia coli for antibacterial activity and Aspergillus flavus, Aspergillus niger and Fusarium oxysporum for antifungal activity. Methods: A mixture of Acid hydrazides (3.0 mmol) and N, N- carbonyl diimidazole (3.3 mmol) in 15 mL of dioxane was refluxed to afford substituted [1, 3, 4]-oxadiazole-2(3H)-one. The resulted [1, 3, 4]- oxadiazole-2(3H)-one (1.42 mmol) was oxidized with Chromyl chloride (1.5 mL) in 20 mL of carbon tetra chloride and condensed with acetophenones (1.42 mmol) to get chalcones 4. The equimolar ratio of obtained chalcones 4 and β -D-1,2,3,4,6- penta-O-acetylglucopyranose in presence of iodine was refluxed to get nucleosides 5. The [1, 3, 4] oxadiazolenone core containing chalcones 4 and nucleosides 5 were tested to determined minimum inhibitory concentration (MIC) value with the experimental procedure of Benson using disc-diffusion method. All compounds were tested at concentration of 5 mg/mL, 2.5 mg/mL, 1.25 mg/mL, 0.62 mg/mL, 0.31 mg/mL and 0.15 mg/mL for antifungal activity against three strains of pathogenic fungi Aspergillus flavus (A. flavus), Aspergillus niger (A. niger) and Fusarium oxysporum (F. oxysporum) and for antibacterial activity against Gram-negative bacterium: Escherichia coli (E. coli), and two Gram-positive bacteria: Staphylococcus aureus (S. aureus) and Bacillus subtilis(B. subtilis). Results: The chalcones 4 and nucleosides 5 were screened for antibacterial activity against E. coli, S. aureus and B. subtilis whereas antifungal activity against A. flavus, A. niger and F. oxysporum. Compounds 4a-t showed good antibacterial activity whereas compounds 5a-t containing glucose moiety showed better activity against fungi. The glucose moiety of compounds 5 helps to enter into the cell wall of fungi and control the cell growth. Conclusion: Chalcones 4 and nucleosides 5 incorporating [1, 3, 4] oxadiazolenone core were synthesized and characterized by various spectral techniques and elemental analysis. These compounds were evaluated for their antifungal activity against three fungi; viz. A. flavus, A. niger and F. oxysporum. In addition to this, synthesized compounds were evaluated for their antibacterial activity against gram negative bacteria E. Coli and gram positive bacteria S. aureus, B. subtilis. Compounds 4a-t showed good antibacterial activity whereas 5a-t showed better activity against fungi.

Background: Tetrapeptide Pro-Ala-Gly-Tyr (PAGY) is an antioxidant peptide that was isolated by Nikoo et al. (2014) from hydrolysate of skin gelatin of amur sturgeon fish (Acipenser schrenckii). This research aims to synthesize PAGY and its analogues by a solid-phase method, and to screen their antioxidant activities. Methods: PAGY and its analogues, namely, Pro-Ser-Gly-Tyr (PSGY), Pro-Ala-Phe-Tyr (PAFY), Pro- Phe-Phe-Tyr (PFFY) and Pro-Ala-Ile-Tyr (PAIY), were synthesized via a solid phase peptide synthesis method with the Fmoc/t-Bu strategy. The synthesis was undertaken on 2-chlorotritylchloride resin as solid support, and all coupling reactions were facilitated by a combination of HBTU and HOBt reagents. All peptides were cleaved from the resin by using 95% TFA in water. Results: Through the solid-phase synthesis method, all peptides were obtained in 50-85% yields. Pure peptides were analysed by analytical RP-HPLC, and were characterized by HR-TOF-ESI-MS and 1HNMR. DPPH inhibition assay was applied to all of the peptides with IC50 of 1.750; 1.116; 1.177 ;1.437; and 1.642 mg/mL for PAGY, PSGY, PAFY, PFFY, and PAIY, respectively. Conclusion: PAGY and its four analogs were successfully synthesized by solid-phase method. PSGY compound was found to have the highest activity of all in DPPH assay.

Background: Many Tunisian medicinal plants are widespread and are used in modern ethnomedecin due to their interesting biological activities. Considering natural products of plant origin, this study was conceived to evaluate the allelopathic effect of leaf and stem extracts of Erica arborea and Viburnum tinus on the seed germination and seedling development of Avena sativa. We identified the secondary metabolites that were responsible. Methods: Total phenols, flavonoids, tannins contents and antioxidant activity were evaluated using the Folin ciocalteux, Aluminum trichloride, vanillin and scavenging activity on 2, 2-diphenyl- 1picrylhydrazyl (DPPH) radicals methods, respectively. Leaf powders (5, 20, 40, 60 and 100 g) were macerated each with 1000 ml of distilled water for 24 h. The extracts were filtered through Whatman N°1 filter paper, pooled and concentrated under vacuum. Allelopathic bioassays were conducted using the obtained supernatant. Results: The obtained results indicated that acetonic extracts of the Viburnum leaves had the highest levels of total phenols (36.82 mg / g), flavonoïds (11.99 mg / g) and tannins (7.93 mg / g) and recorded a high antioxidant activity (0.054 mg / ml). Both test species showed that all organs had significant inhibitory effect on the development of Avena sativa. The leaves of Viburnum are best from the point of view inhibition of root length (-85.45%) and height of the aerial part (-78.95%). Conclusion: The inhibitory effects of these extracts were manifested much more on the development of seedlings. Extracts from Viburnum tinus leaves were the best inhibitors and could be regarded as promising candidates for natural plant source of antioxidant and herbicide agents.

Background: Fluoxetine is a widely prescribed antidepressant that has associated antifungal activity. Methods: This study examined the growth inhibitory and cytotoxic effects of fluoxetine on Candida glabrata. Results: Fluoxetine inhibited growth of C. glabrata on media containing glucose as a carbon source: the inhibition was much greater when ethanol was the carbon source. In hypoosmotic conditions fluoxetine caused death of C. glabrata in one hour. Conclusion: Fluoxetine inhibits fermentative and mitochondrial function of C. glabrata. It rapidly kills C. glabrata in hypoosmotic conditions.

Background: Propolis contains compounds with antibacterial and antioxidant capacities, such as phenolic compounds and flavonoids. The aim of this study was to investigate the antibacterial and antioxidant effects of six propolis samples from northern Morocco and to determine their content of polyphenols and flavonoids. Methods: The total polyphenols and flavonoids of Ethanol Extracts (EEP) were evaluated by colorimetric assays. To test the antibacterial activity, the well diffusion and micro-dilution methods were adopted. The kinetic of bacterial growth in the presence of EEP was tested. The antioxidant activity was evaluated using three techniques: reducing power, β-carotene bleaching test, and DPPH scavenging capacity assay. Results: The EEPs were found to have high total phenolic content (65.09 - 122.00 mg GAE/g) and flavonoids (41.95 - 50.44 mg QE/g). The screening of the antibacterial activity showed that all tested bacteria were sensitive to EEP except Escherichia coli. The inhibitory zones varied from 11.50 ± 0.70 to 32.00 ± 0.70 mm, and MIC and MBC ranged from 0.07 to 5 mg/mL and 0.07 to >5 mg/mL, respectively. The antioxidant activity was proportional to the phenolic content of propolis. The IC50 varied from 48.70 to 156.00 mg/mL and the RAA% ranged from 75.07 to 96.68 %.