The novel economical synthesis and antimicrobial activity of a trithiocarbonate derivative.

The compound diethyl 2,2'-(thiocarbonyl-bis(sulfanediyl))-diacetate 4 belongs to the trithiocarbonate class containing a trithiocarbonate function group flanked by ethyl acetate. In this procedure, a novel economic synthesis route to obtain compound 4 is described. This compound proved to possess broad-spectrum antimicrobial activity both in vitro and in vivo, and could be used as a lead compound. It is worth mentioning that this compound has been patented [No. US 9,988,348 B1; date of patent: June 5, 2018].

Bioactive compounds and health benefits of edible Rumex species-A review.

Medicinal and food plants as well as their bioactive fractions have been used by diverse human cultures since ancient times. These plants provide multiple health benefits because of the presence of a plethora of phytochemicals including phenylpropanoids, isoprenoids, alkaloids, sulphated compounds, peptides and polysaccharides that are responsible for various biological activities such as anticancer, antioxidant, antifungal, antibacterial, anti-dysenteric, anti-inflammatory, antiulcer, anti-hypertensive and anticoagulant properties. The genus Rumex includes edible and medicinal herbs belonging to buckwheat (Polygonaceae) family, consisting of about 200 species rich in phenylpropanoids and anthraquinones. Some Rumex species have exhibited health-promoting effects and have been used as traditional foods and herbal remedies, though a limited information has been documented on their specific biological properties. Therefore, this survey aimed at reviewing the Rumex species with documented biological activity, focusing on preclinical evidences on their efficacy and safety.

Photosynthesis at the far-red region of the spectrum in Acaryochloris marina.

Acaryochloris marina is an oxygenic cyanobacterium that utilizes far-red light for photosynthesis. It has an expanded genome, which helps in its adaptability to the environment, where it can survive on low energy photons. Its major light absorbing pigment is chlorophyll d and it has α-carotene as a major carotenoid. Light harvesting antenna includes the external phycobilin binding proteins, which are hexameric rods made of phycocyanin and allophycocyanins, while the small integral membrane bound chlorophyll binding proteins are also present. There is specific chlorophyll a molecule in both the reaction center of Photosystem I (PSI) and PSII, but majority of the reaction center consists of chlorophyll d. The composition of the PSII reaction center is debatable especially the role and position of chlorophyll a in it. Here we discuss the photosystems of this bacterium and its related biology.

Synthesis and Structure-Activity Relationship of Some New Thiophene-Based Heterocycles as Potential Antimicrobial Agents.

Several new pyrazole, pyridine, [1,2,4]triazolo[1,5-α]pyrimidine, benzimidazo[1,2-a]pyrimidine and 1,2,4-triazolo[3,4-c][1,2,4]triazine derivatives incorporating a thiophene moiety were synthesized from (E)-ethyl 5-(3-(dimethylamino)acryloyl)-4-phenyl-2-(phenylamino)thiophene-3-carboxylate (1). The structures of the newly synthesized compounds were confirmed by IR, ¹H-, (13)C-NMR, mass spectral data and elemental analysis. The antibacterial and antifungal activities of all the synthesized compounds were evaluated. The results indicated that compounds 9, 12, and 19 were found to be more potent than the standard drug Amphotericin B against Aspergillus fumigates. Additionally, compound 12 exhibited higher activity than the standard drug Amphotericin B against Syncephalastrum racemosum.

Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene.

A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS2 in the presence of K2CO3 under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, ¹H-NMR, (13)C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X-ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1-H1···O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1-H2···O1 and C7-H7A···N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong n→π* ICT from LP(1)N5→BD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3→ BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H···OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic.

Synthesis, bioactivity, molecular docking and POM analyses of novel substituted thieno[2,3-b]thiophenes and related congeners.

Several series of novel substituted thienothiophene derivatives were synthesized by reacting the synthone 1 with different reagents. The newly synthesized compounds were characterized by means of different spectroscopic methods such as IR, NMR, mass spectrometry and by elemental analyses. The new compounds displayed significant activity against both Gram-positive and Gram negative bacteria, in addition to fungi. Molecular docking and POM analyses show the crucial role and impact of substituents on bioactivity and indicate the unfavorable structural parameters in actual drug design: more substitution doesn't guaranty more efficiency in bioactivity.

Synthesis, in-vitro antibacterial, antifungal, and molecular modeling of potent anti-microbial agents with a combined pyrazole and thiophene pharmacophore.

Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3a-c, 4, 6a-c and 9a-f were synthesized. The structure of compound 2 was deduced by 1H-NMR, 13C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The compound crystallized in the monoclinic system, with space group P21/c and cell coordinates a = 8.5752(16) Å, b = 21.046(4) Å, c = 8.2941(12) Å, ß = 101.131(6)°, V = 1468.7(4) Å3, and Z = 4. Compounds 2, 3a-c, 4, 5a-c and 9a-f were subjected into in vitro antimicrobial activity tests. Compounds 3a and 3c were more potent than standard drug amphotericin B, showing MIC values of 23.8 ± 0.42 and 24.3 ± 0.68, respectively, against Aspergillus fumigatus while the standard drug MIC was 23.7 ± 0.1. Compound 3c was also more potent (MIC 24.8 ± 0.64) than the standard drug amphotericin B (MIC 19.7 ± 0.2) against Syncephalastrum racemosum. Compounds 4 and 9f also showed promising anti-microbial activity. Molecular modeling was performed for the most active compounds.

Synthesis and biological evaluation of 2-aminobenzamide derivatives as antimicrobial agents: opening/closing pharmacophore site.

A series of new 2-aminobenzamide derivatives (1-10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution.

Computational studies of 2-(4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile.

The molecular structure of the 2-(4-oxo-3-phenylthiazolidin-2-ylidene) malononitrile (3) is calculated using DFT B3LYP/6-311G(d, p) method. The calculated geometric parameters are in good agreement with the experimental data. The NBO calculations were performed to predict the natural atomic charges at the different atomic sites and study the different intramolecular charge transfer (ICT) interactions occurring in the studied system. The BD(2)C17-C19 → BD*(2)C14-C15, LP(2)O2 → BD*(1)N5-C9 and LP(1)N5 → BD*(2)C10-C11 ICT interactions causing stabilization of the system by 23.30, 30.63 and 52.48 kcal/mol, respectively. The two intense electronic transition bands observed experimentally at 249 nm and 296 nm are predicted using the TD-DFT calculations at 237.9 nm (f = 0.1618) and 276.4 nm (f = 0.3408), respectively. These electronic transitions are due to H-3 → L (94%) and H → L (95%) excitations, respectively.

A novel synthesis, X-ray analysis and computational studies of (Z)-ethyl 2-((Z)-5-((dimethylamino)methylene)- 4-oxo-3-phenylthiazolidin-2-ylidene)acetate as a potential anticancer agent.

BACKGROUND: 4-Thiazolidinone ring is reported to have almost all types of biological activities. Also, it present in many marketed drugs. RESULTS: Ethyl acetoacetate reacted with phenyl isothiocyanate and ethyl chloroacetate in presence of K2CO3 and DMF to afford the thiazolidinone derivative 5. Thiazolidinone 5 reacted with dimethylformamide-dimethylacetal to afford (Z)-ethyl 2-((Z)-5-((dimethylamino) methylene)-4-oxo-3-phenylthiazolidin-2-ylidene)acetate (6). The structure of thiazolidinone 6 was elucidated from its spectral analysis and X-ray crystallography and was optimized using B3LYP/6-31G(d,p) method. The geometric parameters and NMR spectra were discussed both experimentally and theoretically. Also, the natural charges at the different atomic sites were predicted. The synthesized compounds had moderate cytotoxic activity. CONCLUSIONS: An unexpected synthesis of (Z)-ethyl 2-((Z)-5-((dimethylamino)methylene)-4-oxo-3-phenylthiazolidin-2-ylidene)acetate via deacetylation mechanism. The structure was established using X-ray and spectral analysis. The geometric parameters, and NMR spectra were discussed. The synthesized compounds showed moderate anticancer activity.

Better agonist for the opioid receptors.

This commentary highlights the recent work published in journal Nature on the structural based discovery of novel analgesic compounds for opioid receptors with minimal effects. Manglik et al. selectively targeted the Gi based µOR pathway instead of the ß-arrestin pathway of the opioids. The computational screening of millions of compounds showed a list of several competent ligands. From these ligands they synthesized the compounds with the best docking score, which were further optimized by adding side residues for better interaction with the µOR. A promising compound, PZM21, was a selective agonist of µOR. It has better analgesic properties with minimal side effects of respiratory depression and constipation. This work is a step towards better drug designing and synthesizing in terms of efficacy, specificity with least side effects of targeted GPCR proteins present in the human proteome.

Honokiol: An anticancer lignan.

BACKGROUND: Honokiol ((3',5-di-(2-propenyl)-1,1'-biphenyl-2,2'-diol), a lignan, is a promising antitumor compound, having exerted activity against a number of human cancer cell lines. Honokiol has inhibitory role on the proliferation, invasion and survival of cancer cells in in vitro as well as in vivo studies. It interferes with signaling pathways components in order to elicit the anticancer effect. SCOPE AND APPROACH: In present review, the published data on the efficacy of honokiol against various cancer cell lines and tumor-bearing animal models has been presented and discussed. KEY FINDINGS AND CONCLUSIONS: Honokiol lowers the expression of pluripotency-factors, the formation of mammosphere, P-glycoprotein expression, receptor CXCR4 level, c-FLIP, steroid receptor coactivator-3 (SRC-3), Twist1, matrix metalloproteinases, class I histone deacetylases, H3K27 methyltransferase among numerous other anticancer functions. It increases bone morphogenetic protein 7 (BMP7), Bax protein, among others. It does so by interfering with the major checkpoints such as nuclear factor kappa B (NF-κB), and activator of transcription 3 (STAT3), mammalian target of rapamycin (m-TOR), epidermal growth factor receptor (EGFR), Sonic hedgehog (SHH). It promotes the efficacy of several anticancer drugs and radiation tolerance. The derivatization of honokiol results in compounds with interesting attributes in terms of cancer control. This review will shed light on the scopes and hurdles in the relevance of the bioactive lignan honokiol in cancer management.

Isolation and Characterization of Two New Antimicrobial Acids from Quercus incana (Bluejack Oak).

Two new compounds [1-2] were purified from ethyl acetate fraction of Quercus incana. The structure of these compounds is mainly established by using advanced spectroscopic technique such as UV, IR, one-dimensional (ID) and two-dimensional (2D) NMR techniques, and EI mass. The structural formula was deduced to be 4-hydroxydecanoic acid [1] and 4-hydroxy-3-(hydroxymethyl) pentanoic acid [2]. Both isolated compounds were tested for their antimicrobial potential and showed promising antifungal activity against Aspergillus niger and Aspergillus flavus.

Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents.

BACKGROUND: The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen. RESULTS: Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity. CONCLUSIONS: Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

Synthesis, characterization, X-ray structure, computational studies, and bioassay of novel compounds combining thiophene and benzimidazole or 1,2,4-triazole moieties.

BACKGROUND: Due to their interesting and versatile biological activity, thiophene-containing compounds have attracted the attention of both chemists and medicinal chemists. Some of these compounds have anticancer, antibacterial, antiviral, and antioxidant activity. In addition, the thiophene nucleus has been used in the synthesis of a variety of heterocyclic compounds. RESULTS: In the present work, two novel thiophene-containing compounds, 4-phenyl-2-phenylamino-5-(1H-1,3-a,8-triaza-cyclopenta[α]inden-2-yl)-thiophene-3-carboxylic acid ethyl ester (3) and 5-(1H-Imidazo[1,2-b] [1,2,4] triazol-5-yl)-4-phenyl-2-phenylamino-thiophene-3-carboxylic acid ethyl ester (4), have been synthesized by reaction of 5-(2-bromo-acetyl)-4-phenyl-2-phenylaminothiophene-3-carboxylic acid ethyl ester (2) with 2-aminobenzimidazole and 3-amino-1H-1,2,4-triazole in the presence of triethylamine, respectively. Compound 2, on the other hand, was prepared by bromination of 5-acetyl-4-phenyl-2-phenylaminothiophene-3-carboxylic acid ester (1). Structures of the newly prepared compounds were confirmed by different spectroscopic methods such as 1H-NMR, 13C-NMR, and mass spectrometry, as well as by elemental analysis. Furthermore, bromination of compound 1 led to the formation of two constitutional isomers (2a and 2b) that were obtained in an 80:20 ratio. Molecular structures of 2b were confirmed with the aid of X-ray crystallography. Compound 2 was crystallized in the triclinic, P-1, a = 8.8152 (8) Å, b = 10.0958 (9) Å, c = 12.6892 (10) Å, α = 68.549 (5)°, ß = 81.667 (5)°, γ = 68.229 (5)°, V = 976.04 (15) Å3, Z = 2, and was found in two isomeric forms regarding the position of the bromine atom. The antibacterial and antifungal activities of the prepared compounds were evaluated. CONCLUSIONS: Three new thiophene derivatives were synthesized in good yield. Antimicrobial screening revealed that compound 3 was a promising candidate as a potential antibacterial and antifungal agent; it exhibits remarkable activity against the studied bacterial strains, especially the gram negative bacteria E. coli in addition to some fungi. More work is needed to evaluate its safety and efficacy.

C,N-bipyrazole receptor grafted onto a porous silica surface as a novel adsorbent based polymer hybrid.

A simple heterogeneous synthesis of pure adsorbent based polymer hybrid made by condensing a functionalized C,N-bipyrazole with a 3-glycidoxypropyl-trimethoxysilane silylant agent, previously anchored on a silica surface was developed. The formed material (SG2P) was characterized through elemental analysis, FT-IR spectroscopy, (13)C NMR of solid state, scanning electron microscope (SEM), and was studied and evaluated by determination of the surface area using the BET equation, the adsorption and desorption capability using the isotherm of nitrogen and B.J.H. pore sizes. The new material exhibits good thermal stability determined by thermogravimetry curves and good chemical stability was examined in various acidic and buffer solutions (pH 1-7). The binding and adsorption abilities of SG2P were investigated for Hg(2+), Cd(2+), Pb(2+), Zn(2+), K(+), Na(+) and Li(+) cations and compared to the results of classical liquid-liquid extraction with the unbound C,N-bipyrazole compound. The grafting at the surface of silica does not affect complexing properties of the ligand and the SG2P exhibits a high selectivity toward Hg(2+) ion with no complexation being observed towards zinc and alkali metals. The extracted and the complexing cation percentages were determined by atomic absorption measurements.

Photosynthesis at the far-red region of the spectrum in Acaryochloris marina

Acaryochloris marina is an oxygenic cyanobacterium that utilizes far-red light for photosynthesis. It has an expanded genome, which helps in its adaptability to the environment, where it can survive on low energy photons. Its major light absorbing pigment is chlorophyll d and it has α-carotene as a major carotenoid. Light harvesting antenna includes the external phycobilin binding proteins, which are hexameric rods made of phycocyanin and allophycocyanins, while the small integral membrane bound chlorophyll binding proteins are also present. There is specific chlorophyll a molecule in both the reaction center of Photosystem I (PSI) and PSII, but majority of the reaction center consists of chlorophyll d. The composition of the PSII reaction center is debatable especially the role and position of chlorophyll a in it. Here we discuss the photosystems of this bacterium and its related biology.

Determination of heavy metals in the fruit of date palm growing at different locations of Riyadh.

Exposure of heavy metals to human beings has risen dramatically in the last 50 years. In today's urban and industrial society, there is no escaping from exposure to toxic chemicals and heavy metals. Humans are more likely to be exposed to heavy metal contamination from the dust that adheres to edible plants than from bioaccumulation. This is because it is very difficult to wash off all the dust particles from the plant material before ingesting them. The objectives of this experiment were to determine the concentrations of lead (Pb) and cadmium (Cd) in washing residues and in the tissues of fruits of date palm growing in 14 sites of Riyadh and also to assess whether the fruits were safe for human consumption. The washing residues and tissue of date palm fruits collected from different sites showed the presence of significant amounts of the Pb and Cd. The concentration of Pb in the dust and fruit tissue increased with increasing anthropogenic sources. Therefore, fruits of date palm might be used as a pollution indicator; it might be recommend that fruits of date palm could be safe for human consumption after washing. The mean concentration of Pb and Cd in all the samples collected from different sites is within the safe limits recommended by FAO/WHO.