Current Bioactive Compounds - Volume 16, Issue 2, 2020

Background: According to the World Health Organization (WHO), the routine use of antibiotics has led to the increase of microbial resistance. Thus, the search for new compounds that present antimicrobial activity must be constant. This study reports the bactericidal activity assay of the steviol derivative 17-hydroxy-16-hydroxyiminobayeran-19-oic acid against various bacteria and structural studies by quantum chemistry and molecular dynamics. Methods: Bactericidal activity assays of the steviol derivative 17-hydroxy-16-hydroxyiminobayeran-19- oic acid against Salmonella typhimurium [ATCC 14028], Staphylococcus aureus [ATCC 6538], Bacillus cereus [ATCC 11778], Helicobacter pylori [ATCC 26695], Pseudomonas aeruginosa [ATCC 27853], Escherichia coli [ATCC 25922] and Bacillus subtilis [ATCC 23857] were performed, as well as structural studies by quantum chemistry and molecular dynamics. Results: The results show that the compound exhibits activity towards S. typhimurium, what makes it an interesting compound for future studies on the development of antibiotics against this bacteria. An intramolecular hydrogen bond does not seem to be maintained in solution, therefore, corresponding moieties should be prone to interactions with their surroundings. Conclusions: The results indicate that the title compound exhibits activity towards S. typhimurium, what sums up to similar results from other steviol derivatives and stevioside, thus reinforcing the potential of these compounds for future studies on the development of antibiotics against this bacteria. The potential energy surface for the selected torsion angles and molecular dynamics have revealed that an intramolecular hydrogen bond, though slightly energetically favorable, does not seem to be maintained in solution; therefore, corresponding moieties should be prone to interactions with their surroundings, an important feature in further studies involving inhibitor/drug design from this compound.

Background: Ultraviolet B (UV-B) radiation is a promising and environmentally friendly technique, which in a low flow rate, can induce bioactive compound synthesis. This work aimed at evaluating the effectiveness of post-harvest UV-B treatment in order to improve carotenoid content in climacteric fruits like persimmon and guava fruits. Methods: The fruits were harvested at commercial maturity and placed into climatic chambers equipped with UV-B lamps. For control treatment, the UV-B lamps were covered by a benzophenone film, known to block the radiation. This radiation was applied during 48 hours and fruits were sampled at 25, 30 and 48 hours of each treatment. HPLC analysis was performed to separate and identify carotenoid compounds from fruit skin after a saponification process. Results: Fruit from 30 hours treatment began to present a carotenoid accumulation since the majority of analyzed compounds exhibited its synthesis stimulated from this time on. In persimmon skin, it was observed that the maximum content was reached after 48 hours of UV-B treatment. Conclusion: These results suggest that this post-harvest UV-B treatment can be an innovative and a viable method to induce beneficial effects on guava and mainly on persimmon fruit.

Objective: In this work, we investigated the chemical composition and the antioxidant and antimicrobial activities of the Algerian Cistus clusii Dunal essential oil. Methods: Cistus clusii essential oil has been extracted using hydrodistillation method and characterized by GC/MS. The antioxidant activity was evaluated by two different methods DPPH free radical scavenging, and β-carotene bleaching test. The antimicrobial activity was carried out using disc diffusion method against reference strains; Pseudomonas aeruginosa (ATCC 27865), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), clinical bacterial (Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus) and fungal (Candida albicans) isolates. Results: The chemical profile of the oil showed 31 compounds. This profile was dominated by the presence of monoterpene hydrocarbons (78.4%), oxygenated derivatives (18.8%) and sesquiterpene hydrocarbons as minor constituents of this essential oil (1.9%). The major constituents were Camphene (20.6%), γ-Terpinene (16.5%), Sabinene (12.8%), and Terpineol-4 (13.5%). Other compounds were found in moderately good amounts like α-Terpinene (8.9%), α-Thujene (5.9%), α-Pinene (4.2%), and α- Terpinolene (3.1%). The results of the antimicrobial activity showed that the highest activity was observed against C. albicans and it was higher than positive control Fluconazole. The essential oil exhibited a strong antioxidant activity, especially in the β-carotene system. Conclusion: This study indicates that Cistus clusii essential oil showed potent antioxidant and moderate antimicrobial activities which could be used to explain the use of this species in traditional medicine.

Background: The development of resistance by pathogenic microorganisms has renewed the worldwide search for novel antimicrobial agents. Mushrooms are of recent interest because a wide variety of biologically active compounds have been isolated from them. This study isolated antimicrobial compound from two wood decaying mushrooms, Trametes gibbosa and Trametes elegans, and determined the resistance modifying activities of the isolated compound. Methods: Bioactivity guided isolation of active principles from the methanol extract of T. gibbosa and T. elegans was performed using column and preparative high-performance liquid chromatography. The structures of isolated compounds were elucidated using nuclear magnetic resonance spectroscopy. Broth micro-dilution assay was used to determine the antimicrobial and resistance modifying activities of the isolated compounds against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Streptococcus pyogenes, Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Candida albicans, Aspergillus niger, Aspergillus flavus and Aspergillus tamarii. Results: Bioactivity guided isolation lead to the isolation of cerevisterol (ergosta-7, 22E-diene-3β5α, 6β- triol) from both T. gibbosa and T. elegans. The isolated cerevisterol inhibited the growth of S. typhi, S. aureus and A. niger with MICs of 25 μg/mL each and 50 μg/mL against E. faecalis. The MBCs of cerevisterol against S. typhi S. aureus, E. faecalis and A. niger were 50, 100, 200 and 100 μg/mL, respectively. The sub-inhibitory concentration (3 μg/mL) of cerevisterol modified the activity of erythromycin, ampicillin, ciprofloxacin, tetracycline and amoxicillin either by potentiating or reducing their activities. Conclusion: Cerevisterol possesses both antimicrobial and resistance modifying activities.

Background: Dittrichia graveolens (L.) is a strongly aromatic plant distributed in Mediterranean regions. This research concerns the optimization of the Total Phenolic Content (TPC) and the Total Tannin Content (TTC) of Dittrichia graveolens (L.) extracts using Response Surface Methodology for Ultrasound Assisted Extraction (UAE) and Microwave Assisted Extraction (MAE). Central Composite Design (CCD) was used to evaluate the effect of the solvent concentration and the extraction time, in different methods on TTC and TPC. The antioxidant activities and antibacterial activities were evaluated. Methods: The plant extracts were prepared using maceration, microwave and ultrasound assisted extraction. TPC and TTC were measured using Folin-Ciocalteu method. The antioxidant activities were studied using DPPH reagent and disc diffusion method was used to study the antibacterial activities. Results: This study showed the optimum condition for UAE was 49.96% methanol concentration and 11.2 min sonication, while for MAE was 55.44% methanol concentration and 2.26 min microwave extraction. It also indicated that MAE was the most effective method in comparison to UAE and maceration. The antioxidant activities of MAE extract (IC50=7.7mg/mL) were more than UAE extract (IC50=21.5mg/mL) and maceration (IC50=32.3mg/mL). Conclusion: As a conclusion, it was indicated that MAE was the most effective method. The higher total phenolic content caused higher antioxidant activities as MAE extract had the highest antioxidant activities. The antibacterial test showed the great potential of this plant as an antibacterial compound resource against different bacteria.

Background: Cancer is a major health problem acting as a global killer and one of the leading causes of death. Most cancer chemotherapeutic drugs currently in clinical use are to kill malignant tumour cells by inhibiting some of the mechanisms implied in cellular division. Thienopyrimidines occupy a special position among the fused pyrimidines, along with other pyrimidines containing an annelated five membered hetero aromatic ring; forms a significant class of drugs which exhibit an array of various biological activities. One of the important current anticancer agent gefitinib acts as tyrosine kinase inhibitors is a quinazoline derivative. The thieno[2,3-d]pyrimidine ring system, is considered as a bioisostere of quinazoline moiety and have attracted great attention due to their broad bioactivities, including antitumor. Methods: Novel thienopyrimidine derivatives were synthesized by cyclization of thiophene o-amino esters with lactam salts such as pyrrolidin-2-one, piperidin-2-one and caprolactam by treating using phosphorous oxychloride. The next set of compounds thieno[2,3-d]pyrimidin-4(3H)-one were synthesised by Niementowski condensations between 2-aminothiophene carboxylate and formamide under reflux condition, followed by its chlorination in good yield. Microwave Fusion of 4-chlorothieno[2,3-d] pyrimidines with o-phenylenediamine afforded target compounds. The target compounds were tested on MCF-7 and HEK293 cell line. Results: The synthesized thirty compounds structures were established by IR, 1H NMR and Mass spectroscopy. The synthesized compounds were obtained in the good yield ranging from 45-70%. The synthesized compounds were subjected to cytotoxicity studies. Among the twenty compounds only one compound showed moderate activity. One of the compound 2c bearing acetyl group had IC50 48.93 μM. However decrease in the size of the lactam ring from six to five member ring or increase to seven member ring resulted in the loss of activity. The IC50 value of 5a was found to be 70.86μg/ml. The compound 5i have more cytotoxic action among the series. Conclusion: A series of thirty compounds belonging to novel pyyrolo, pyrido and benzimidazole fused thienopyrimidines were synthesized, characterized and were evaluated for their in vitro cytotoxicity. The compounds bearing bulky group such as terbutyl group and chloro substitution had the best activity. In conclusion, these structures seems to have biological properties and further investigation on this group could provide a lead.

Background: The 8-Aminoquinoline (8-AQ) framework has attracted particular attention in the discovery and development of antimalarial and anti-bacterial agents or drugs. However, the clinical uses of 8-AQ based drugs are often associated with toxic side effects such as methemoglobinemia and hemolytic anemia with deficiency in Glucose-6-Phosphate Dehydrogenase (G6PD) Activity. The 4-aryl- 8-amino(acetamido)quinoline derivatives, on the other hand, have shown antiproliferative activities against cancer cell lines. These reports prompted us to assess the antibacterial and cytotoxic activities of a series of compounds based on 5-aryl 8-aminoquinoline amide scaffold. Methods: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized via a one-pot ultrasound-assisted method using a C-5 selective halogenation of quinoline derivatives followed by Pd/C-catalyzed Suzuki-Miyaura coupling with (het)aryl boronic acids. All these compounds were evaluated for their in vitro antibacterial activities against representative Gram-(+) and Gram-(-) strains including Escherichia coli, Pseudomonas aeruginosa, Klebsiella species and Staphylococcus aureus. Three compounds were further tested for cytotoxicities in vitro against breast adenocarcinoma (MCF7) and Hepatocellular Carcinoma (HepG2) along with non-cancerous human embryonic kidney (HEK293) cell lines. Results: All these compounds demonstrated moderate to good antibacterial activities against the four organisms used. In vitro assay results revealed that three compounds showed good activities against Gram-(+) strains and Gram-(-) strains and one was comparable to ciprofloxacin and pefloxacin. These three compounds were further tested for their cytotoxic properties against MCF7 and HepG2 cell lines. One of them showed IC50 value comparable to doxorubicin when tested against HepG2 cell lines. However, none of these compounds showed any significant effects when tested against HEK293 cells indicating their selectivity towards the growth inhibition of cancer cells. Conclusion: A series of compounds based on 5-(het)aryl 8-aminoquinoline amide scaffold was synthesized and evaluated for antibacterial and cytotoxic activities. Several of these compounds showed promising antibacterial and cytotoxic activities when tested in vitro suggesting that the present class of compounds may be of interest for the identification of new and potential antibacterial / cytotoxic agents.

Background: Mangrove plant extracts are used in folkloric medicine as aphrodisiac, sedative, antioxidant, antimicrobial and antimalarial. Screening for antimicrobial, phytochemical and antioxidant activities of fourteen mangroves plant species (Aegiceras corniculatum, Acanthus ilicifolius, Avicennia alba, Avicennia marina, Avicennia officinalis, Bruguiera cylindrica, Bruguiera gymnorhiza, Ceriops tagel, Excoecaria agallocha, Kandelia candel, Rhizophora apiculata, Rhizophora mucronata, Sonneratia alba, and Sonneratia caseolaris) in various solvents are reported in this work. Methods: The antimicrobial screening was carried out using agar well diffusion method. In this study, nine pathogenic strains were used, including three Gram-positive and six Gram-negative bacteria. Phytochemical screening, total flavonoids, total phenolic and antioxidant activity was tested by DPPH radical scavenging assay. Four phenolic compounds (gallic acid, vanillin, tannic acid and quercetin) were quantified by LC-MS/MS in selected mangrove species. Results: Antimicrobial screening showed Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa were most susceptible to ethyl acetate extract as compared to ethanol and methanol extract. Ethyl acetate extract of Avicennia marina and Bruguiera gymnorhiza showed strong antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa. Phytochemical analysis revealed the presence of saponins, phenolics, flavonoids, alkaloids, tannins, and terpenoids, which was found to be variable as per the solvent used for extraction. In addition, total phenolics and total flavonoids content with different solvents were found in the range of 11.08 to 196.76 mg GAE/g and 12.92 to 110.3 mg QE/g of extract respectively. Moreover, antioxidant capacities expressed in terms of IC50 (mg/mL) showed that methanol extract exhibited higher antioxidant capacity followed by ethanol extract. LC-MS/MS analysis showed gallic acid and tannic acid are present in higher concentration in Aegiceras corniculatum and Sonneratia caseolaris than other species. The vanillin and quercetin were found in the least concentration. Conclusion: Mangroves species are rich source of antioxidant, phenolics and antimicrobial compounds.

Background: Cotula cinerea belongs to the Asteraceae family and grows in desert areas such as Moroccan Sahara. The use of this plant in Moroccan traditional medicine prompted us to investigate its chemical composition, its acute oral toxicity, its analgesic and antioxidative activities. Methods: Extraction was conducted by steam distillation for essential oil and by maceration using solvents (hexane, ethyl acetate, n-butanol) for other non-volatile compounds. Quantitative analysis of total polyphenols, procyanidins and flavonoids was conducted through spectrophotometric assays. Qualitative phytochemical composition of the essential oil was investigated by GC/MS analysis. Acute oral toxicity was tested at a dose of 2000 mg/kg in mice. Central analgesic effect was assessed in rat using tail flick and hot plate models and the obtained results were compared to morphine. Antioxidant activity of the essential oil and the obtained extracts was evaluated through 2,2-diphenyl-1- picrylhydrazyl (DPPH°) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and the obtained results were compared to TROLOX. Results: The obtained results showed that the studied extracts contained significant amounts of total polyphenols, flavonoids and condensed tannins. The phytochemical composition of the essential oil was predominated by thujone, eucalyptol and santolinatriene. The results of the acute oral toxicity showed that the tested essential oil and extracts were not toxic even at the highest dose of 2000 mg/kg. Experiments on analgesic activity showed that the administered extracts have a central analgesic effect. The highest effect was observed with the n-butanol and ethyl acetate extracts for both tail-flick and hot plate tests. The antioxidant activity of the explored extracts showed higher scavenging activities of the studied samples compared to TROLOX. Conclusion: Our results indicate thus that C. cinerea could be considered as a source of various secondary metabolites including terpenoids and polyphenols. Exploration of its biological activities showed that the plant essential oil and extracts possessed antioxidant and analgesic effects. Based on the results of this study, it is likely that extracts of C. cinerea could open perspectives for its use for pain relief.

Background: The ability of Centaurea maroccana (C. maroccana) and Centaurea acaulis (C. acaulis) to protect the kidney against CCl4-induced renal toxicity in male rats was investigated. Moreover, the total polyphenols and flavonoids amount and DPPH radical scavenging activity were estimated. Materials and Methods: Rats were pre-treated orally with C. maroccana and C. acaulis (200 mg/kg, daily for 2 weeks) along with CCl4 (1.5 ml/kg, three times a week for 2 weeks). At the end of the treatment procedure, all rats were sacrificed and renal protective effect of C. maroccana and C. acaulis was evaluated. Results: Administration of CCl4 alone significantly elevated kidney malondialdehyde, as well as serum creatinine, urea and uric acid. While kidney level of glutathione and catalase were reduced. These were accompanied by glomerular and tubular degenerations and necrosis. Pre-treatment with C. maroccana and C. acaulis ameliorated the above mentioned biochemical parameters and histological changes associated with nephrotoxicity induced by CCl4. Moreover, both studied extracts showed a noticeable total polyphenols and flavonoids amount and antioxidant activity in DPPH assays. Conclusion: From the results, it is suggested that C. maroccana and C. acaulis extract has the ability to protect kidney against oxidative damages, possibly through the antioxidant effects of their bioactive compounds.