Microbial exopolysaccharide production of Streptococcus thermophilus and its antiquorum sensing activity.

Interest in the production of exopolysaccharides by microorganisms has increased in the recent years. Using low-cost product is the main step of microbial production to reduce cost and compete with chemical production. In this work, EPS production of Streptococcus thermophilus isolates from yogurt (S2), kefir (S3), and S. thermophilus ATCC 19258 (S1) isolate which was used as control strains were investigated by using different fruit pulps. S. thermophilus isolates were identified by morphological and 16S sequence analysis. The amount of EPS obtained was measured spectrophotometrically using glucose as standard with phenol sulfuric acid method. All three isolates produced higher amounts of EPS on M17 medium than Nutrient medium. When the fruit pulp was added to the medium, EPS production increased in all three isolates. When different nitrogen sources were added together with fruit pulp juice, EPS production increased. The highest amount of EPS produced by ATCC 19258 strain (21.570 mg/L) and S3 isolate (29.131 mg/L) is the medium where mixed fruit pulp juice and nitrogen source is tryptophan. It has been shown that EPS production is increased by adding fruit pulps to the prepared media. It is thought that apricot pulp can be a good alternative in EPS production especially in the evaluation of wastes. Also, antiquorum sensing activity of the highest amount EPS was determined by using Chromobacterium violaceum CV026 strain and found effective on violacein pigment inhibition and C6-AHL production of biosensor strain.

Synthesis and Structure Elucidation of New Benzimidazole Amidoxime Derivatives.

OBJECTIVES: In our previous studies we synthesized some potent antiparasitic, anticancer and antimicrobial amidine derivatives. Despite all their potent activities, it is well known that due to their cationic charge, amidine derivatives pose a serious problem in terms of bioavailability. The main purpose of this study is to prepare amidoxime derivatives of previously synthesized potent amidine derivatives as prodrugs in order to increase their bioavailabilities. MATERIALS AND METHODS: The targeted benzimidazole amidoximes were synthesized from their nitrile derivatives. The nitrile groups of these benzimidazole carbonitriles were converted to N-hydroxy benzamidine derivatives (amidoxime derivatives, 20-29) in the presence of NH2OH.HCI and KO-t-Bu in dimethyl sulfoxide. Structures of newly synthesized amidoxime derivatives were elucidated with 1H-NMR, 13C-NMR and some 2D NMR techniques like COSY, NOESY, HSQC and HMBC. RESULTS: A new series of benzimidazole amidoximes were synthesized and their structural elucidations were done in this study. CONCLUSION: In order to solve the potential bioavailability problem of potent amidine derivatives, we prepared the prodrugs of those potent amidine derivatives as their amidoxime derivatives. In vivo studies of both previous amidine derivatives and amidoxime prodrugs of those amidines which were synthesized in this study are planned to perform in our ongoing studies.

Synthesis & Anticancer Evaluation of New Substituted 2-(3,4- Dimethoxyphenyl)benzazoles.

BACKGROUND: The benzazole nucleus is found in many promising small molecules such as anticancer and antibacterial agents. Bendamustine (Alkylating agent), Nocodazole (Mitotic inhibitor), Veliparib (PARP inhibitor), and Glasdegib (SMO inhibitor) are being clinically used as anticancer therapeutic which bear benzimidazole moiety. Based on the principle of bioisosterism, in the present work, 23 compounds belonging to 2-(3,4-dimethoxyphenyl)benzazoles and imidazopyridine series were synthesized and evaluated for their anticancer and antimicrobial activities. OBJECTIVE: A series of new 2-(3,4-dimethoxyphenyl)-1H-benz(or pyrido)azoles were synthesized and evaluated for their anticancer and antimicrobial activities. METHOD: N-(5-chloro-2-hdroxyphenyl)-3,4-dimethoxybenzamide 1, was obtained by the amidation of 2-hydroxy-5-chloroaniline with 3,4-dimethoxybenzoic acid by using 1,1'-carbonyldiimidazole. Cyclization of 1 to benzoxazole derivative 2, was achieved by p-toluenesulfonic acid. Other 1H-benz(or pyrido)azoles were prepared by the reaction between 2-aminothiophenol, ophenylenediamine, o-pyridinediamine with sodium metabisulfite adduct of 3,4-dimethoxybenzaldehyde. The NMR assignments of the dimethoxy groups were established by the NOESY spectra. RESULTS: Compound 12, bearing two chlorine atoms at the 5(4) and 7(6) positions of the benzene moiety of benzimidazole was found the most potent analogue against A549 cells with the GI50 value of 1.5 µg/mL. Moreover, 24 showed remarkable cell growth inhibition against MCF-7 and HeLa cells with the GI50 values of 7 and 5.5 µg/mL, respectively. The synthesized compounds have no important antibacterial and antifungal activities. CONCLUSION: It could be concluded that the introduction of di-chloro atoms at the phenyl ring of 2-(3,4-dimethoxyphenyl)-1H-benzimidazoles increases significant cytotoxicity to selected human tumor cell lines in comparison to other all benzazoles synthesized. Unsubstituted 2-(3,4- dimethoxyphenyl)-imidazopyridines also gave good inhibitory profile against A549 and HeLa cells.

Antiproliferative activity of synthesized some new benzimidazole carboxamidines against MCF-7 breast carcinoma cells.

Breast cancer is the most endemic cause of cancer among women in both developed and developing countries. Benzimidazole derivatives exemplify one of the chemical classes that show strong cytotoxic activity especially against breast cancer cells (MCF-7). Aromatic amidine derivatives are known as a group of DNA interactive compounds that bind minor groove of the genome, especially A-T base pairs, and show significant in vitro and in vivo toxicity toward cancer cells. In light of these studies, some new mono/dicationic amidino benzimidazole derivatives were synthesized and evaluated for cytotoxic activity on cultured MCF-7 breast cancer cells. Some of these compounds have strongly inhibited MCF-7 cell viability in a dose-dependent manner compared with clinically used reference compounds, imatinib mesylate and docetaxel. Among them, 4-[(5(6)-bromo-1H-benzimidazole-2-yl)amino]benzene-1-carboxamidine (30) showed the best inhibitory activity with IC50 value of 4.6 nM.

Synthesis and potent antiprotozoal activity of mono/di amidino 2-anilinobenzimidazoles versus Plasmodium falciparum and Trypanosoma brucei rhodesiense.

A series of mono and dicationic new 2-anilinobenzimidazole carboxamidines were prepared in a four step process starting from 4-amino-3-nitrobenzonitrile and corresponding o-phenylenediamines. Their antiparasitic activity against Plasmodium falciparum (P. falciparum) and Trypanosoma brucei rhodesiense (T.b. rhodesiense) were evaluated in vitro. Some of the dicationic compounds (10,12,14) showed equal or very close activity against T.b. rhodesiense with melarsoprol and also showed promising activity against P. falciparum as compared to chloroquine. Among the monocationic derivatives compound 21 exhibited best inhibitory activity against P. falciparum.

Novel indole-based melatonin analogues: Evaluation of antioxidant activity and protective effect against amyloid ß-induced damage.

Oxidative stress has been recognized as a contributing factor in ageing and various diseases including cancer and neuropathological disorders. Indole derivatives such as the neurohormone melatonin (MLT) constitute an important class of therapeutic agent in medicinal chemistry. MLT can scavenge different reactive oxygen species and can also stimulate the synthesis of antioxidant enzymes. As a part of our ongoing studies, a series of new indole-based hydrazide/hydrazone derivatives were synthesized as MLT analogues. Their antioxidant activity was investigated in human erythrocytes by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Possible inherent cytotoxicity of the compounds was investigated in CHO-K1 cells by lactate dehydrogenase leakage test. Protection of neuronal PC12 cells against amyloid ß-induced damage was examined by MTT assay and their ability in reduction of ROS generation induced by amyloid ß was tested. MLT analogues having an o-halogenated aromatic moiety exhibited effective antioxidant properties without having any membrane-damaging effect. Moreover, derivatives having o-halogenated and dihalogenated aromatic side chain significantly protected neuronal cells at concentrations of 10 and 100 µM. In conclusion, MLT derivatives represent promising scaffolds for discovery of effective antioxidant and neuroprotective agents.

Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents.

A series of novel polyhalogenated 2-phenylbenzimidazoles have been synthesized and evaluated for in vitro antistaphylococcal activity against drug-resistant bacterial strains (methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. Certain compounds inhibit bacterial growth perfectly. 11 was active than vancomycin (0.78 µg/mL) with the lowest MIC values with 0.19 µg/mL against methicillin-resistant Staphylococcus aureus, 8 and 35 exhibited best inhibitory activity against vancomycin-resistant Enterococcus faecium (1.56 µg/mL). The mechanism of action for this class of compounds appears to be different than clinically used antibiotics. These polyhalogenated benzimidazoles have potential for further investigation as a new class of potent anti-methicillin-resistant Staphylococcus aureus and anti-vancomycin-resistant Enterococcus faecium agents.

Antioxidant properties of melatonin and its potential action in diseases.

In recent years, relationship between free radicals and oxidative stress with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases became increasingly clear. Confirming the role of oxidants in numerous pathological conditions such as cancer, the antioxidants developed as therapeutics have been proven ineffective. It is well established that melatonin (MLT) and its metabolites are able to function as endogenous free-radical scavengers and broadspectrum antioxidants. Numerous studies also proved the role of MLT and its derivatives in many physiological processes and therapeutic functions, such as the regulation of circadian rhythm and immune functions. The aim of this review is to arouse attention to MLT as a potentially valuable agent in the prevention and/or treatment of some diseases.

Synthesis and antioxidant properties of substituted 2-phenyl-1H-indoles.

In this study, we report the design, synthesis and antioxidant activity of a series of substituted 2-(4-aminophenyl)-1H-indoles and 2-(methoxyphenyl)-1H-indoles. The new compounds are structurally related to the known indole-based antioxidant lead compound melatonin (MLT), and the antitumour 2-(4-aminophenyl)benzothiazole and 2-(3,4-dimethoxyphenyl)benzothiazole series. Efficient access to the target 2-phenylindoles was achieved via Fischer indole synthesis between substituted phenylhydrazines and acetophenones. 2-(4-Aminophenyl)indoles (such as the 6-fluoro analogue 3b) in particular showed potent antioxidant activity in the DPPH and superoxide radical scavenging assays (80% and 81% inhibition at 1mM concentration of 3b, respectively), at a level comparable with the reference standard MLT (98% and 75% at 1 mM).

Potent antifungal and antistaphylococcal 2-anilinobenzimidazoles.

A series of 21 anilinobenzimidazoles with a 2,4-difluorophenyl group were synthesized and their minimum inhibitory concentrations (MIC) determined by the tube dilution method. Most of the compounds exhibited excellent MIC values against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Among them, compound 27 having dibromo substitution at the 4- and 6-position of the benzimidazole ring showed the best antifungal activity against Candida krusei with a MIC value of 3.12 microg/mL that surpassed that of the reference drug fluconazole.