Polyethylene Glycol-400 Prompted an Efficient Synthesis of Thienyl Pyrazolo[ 1,5-a] Pyrimidines as Microbial Inhibitors.

AIMS: The aim of this present work was to design and establish an efficient synthesis of new thienyl pyrazolo[1,5-a] pyrimidines using an environmentally friendly reaction solvent. Further, the newly synthesized compounds were evaluated for antimicrobial activity. MATERIALS AND METHODS: A series of thienyl pyrazolo[1,5-a] pyrimidines have been synthesized by the condensation reaction of 4-(4'-chloro-phenylazo)-5-amino pyrazole with α, ß- unsaturated carbonyl composites (chalcones) using NaOH in polyethylene glycol- 400 as a green reaction solvent. The dissemination technique recommended by the National Clinical Laboratory Standards Committee was used to study the antimicrobial activities of synthesized compounds. RESULTS AND DISCUSSION: Polyethylene glycol-400 prompting an efficient synthesis of thienyl pyrazolo[1,5-a] pyrimidines have been discussed. Excellent yields of the products were obtained in a shorter reaction time using PEG 400 as a green reaction solvent. The reaction solvent was recovered and reused without the loss of its activity. The synthesized compounds have shown interesting antibacterial activity. Hydroxyl and halo substitution with thienyl moiety emerged as an active antibacterial and antifungal study. CONCLUSION: The advantage of this methodology is that it incorporates the green method, has excellent yields, easy workup, avoids toxic solvents, and an expensive catalyst. The new dimension pyrazolo[1,5-a] pyrimidine derivatives with thienyl moiety exhibit promising anti-microbial activity.

Novel Gomisin B analogues as potential cytotoxic agents: Design, synthesis, biological evaluation and docking studies.

As part of pharmacological-phytochemical integrated studies on medicinal flora, Gomisin B (1) was isolated as major phytochemical lead from schisandra grandiflora, a plant traditionally used in different Asian systems of medicine. A series of 1,2,3-triazoles derivatives were synthesized at the C-7' position of the gomisin B core through diastereoselective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5q) were well characterized using modern spectroscopic techniques and evaluated for their anti-cancer activity against a panel of five human cancerous cell-lines. Among them, compound 5b exhibited the best cytotoxicity against SIHA cell (IC50 0.24 µM) which was more than the standard drug doxorubicin, while the other derivatives were exhibited moderate to low activities in tested cell lines. The cell cycle analysis indicated that compound 5b stalled HeLa cells at G2/M phase. 5b promoted tubulin polymerization and this was supported by the docking studies, wherein 5b showed significant binding affinity at the colchicine binding pocket of tubulin. Overall, we identified a novel small molecule that demonstrated anticancer activity by promoting in vitro tubulin assembly.

"Click" reaction mediated synthesis of costunolide and dehydrocostuslactone derivatives and evaluation of their cytotoxic activity.

As part of pharmacological-phytochemical integrated studies on medicinal plants from Indian flora, costunolide (1) and dehydrocostus lactone (2), were isolated as major phytochemicals from Saussurea lappa, a plant traditionally used in different Asian systems of medicine. A series of 1,4-disubstituted-1,2,3-triazoles conjugates were synthesized through diastereo selective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5j) & (7a-7j) were well characterized using modern spectroscopic techniques and evaluated for their anticancer activity against a panel of five human cancerous celllines. The results indicated that all the analogs displayed moderate cytotoxic activity.

Novel sesquiterpenes from Schisandra grandiflora: isolation, cytotoxic activity and synthesis of their triazole derivatives using "click" reaction.

Phytochemical investigation of hexane extract from the fruits of Schisandra grandiflora afforded three novel sesquiterpenes (1-3) along with the three known compounds (4-6). The structures of these isolates were determined by extensive analysis of spectroscopic data (1D, 2D NMR). Further, a series of triazole analogues of 3 and 4 were prepared using "Click" reaction protocol. The reaction scheme involving one-carbon homologation of 3 and 4 using the Bestmann-Ohira reagent followed by regioselective Huisgen 1,3-dipolar cycloaddition reaction of various azides leading to the formation of triazole analogues (20a-20k &21a-21c) which is being reported for the first time. All the triazole products were characterized using spectral data analysis. The anti-proliferative activity of the isolates and the synthetic analogues were studied against Hela (Cervical cancer), A549 (Lung cancer), DU-145 (Prostate cancer), MCF-7 (Breast cancer) and B-16 (Mouse melanoma) cancer cell lines.

Effect of operational parameters on heavy metal removal by electrocoagulation.

In the present paper, the performance of electrocoagulation (EC) for the treatability of mixed metals (chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn)) from metal plating industrial wastewater (EPW) has been investigated. The study mainly focused on the affecting parameters of EC process, such as electrode material, initial pH, distance between electrodes, electrode size, and applied voltage. The pH 8 is observed to be the best for metal removal. Fe-Fe electrode pair with 1-cm inter-electrode distance and electrode surface area of 40 cm(2) at an applied voltage of 8 V is observed to more efficient in the metal removal. Experiments have shown that the maximum removal percentage of the metals like Cr, Ni, Zn, Cu, and Pb are reported to be 96.2, 96.4, 99.9, 98, and 99.5 %, respectively, at a reaction time of 30 min. Under optimum conditions, the energy consumption is observed to be 51.40 kWh/m(3). The method is observed to be very effective in the removal of metals from electroplating effluent.

Limonoids from the leaves of Soymida febrifuga and their insect antifeedant activities.

Three new phragmalin-type limonoids (1-3) were isolated from the leaves of Soymida febrifuga together with thirteen known limonoids. The structures of these compounds were established on the basis of spectroscopic data. All these isolates were evaluated for their anti-feedant activities in tobacco caterpillar (Spodoptera litura) and castor semilooper (Achaea janata) using a no-choice laboratory bioassay. Among the tested, compounds 9 and 15 demonstrated the potent anti-feedant index (76.46 µg/cm(2), 66.61 µg/cm(2) against A. janata, and 61.69 µg/cm(2), 51.93 µg/cm(2)against S. litura).

Synthesis, anticancer, and antibacterial activities of piplartine derivatives on cell cycle regulation and growth inhibition.

A series of piplartine derivatives were synthesized via Baylis-Hillman reaction and evaluated for anticancer and antibacterial activities. The cytotoxicity of these compounds was examined in two different human tumor cell lines, IMR-32 and HeLa. The antibacterial activity was examined in Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that compounds 2b, 2e, and 2j were found to be the most active compounds, which displayed line no cytotoxicity, but G2-M cell cycle arrest in tumor cells, and showed cytostatic effects in bacteria.

Synthesis and antimicrobial activity of novel pyrazolo[3,4-d]pyrimidin derivatives.

Pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives have been prepared by cyclocondensation of ethyl 2-cyano-3,3-bis(methylthio)prop-2-enoate with 2-amino-4-(substitutedphenyl)thiazole to give 3-cyano-2-methylthio-4-oxo-4H-6-(substitutedphenyl)thiazolo[3,2-a]pyrimidin (2a-j) and further reacting with hydrazine hydrate to yield the target compounds (3a-j). The chemical structure of the compounds was confirmed by IR and (1)H NMR spectral data. All the compounds of the series have been screened for their antibacterial and antifungal activity studies. The result revealed that all compounds showed significant antimicrobial activity.

Poly(ethylene glycol) (PEG-400) as an alternative reaction solvent for the synthesis of some new 1-(4-(4'-chlorophenyl)-2-thiazolyl)-3-aryl-5-(2-butyl-4-chloro-1H-imidazol-5yl)-2-pyrazolines and their in vitro antimicrobial evaluation.

Several 1-(4-(4'-chlorophenyl)-2-thiazolyl)-3-aryl-5-(2-butyl-4-chloro-1H-imidazol-5yl)-2-pyrazoline derivatives were prepared by the base catalyzed treatment of appropriate chalcones with 4-(4'-chlorophenyl)-2-hydrazino-thiazole in poly (ethylene glycol) (PEG-400) as an alternative reaction solvent. All the synthesized compounds were tested for their antimicrobial activities against Escherichia coli (MTCC 2939), Salmonella typhi (MTCC 98), Staphylococcus aureus (MTCC 96), Bacillus subtilis (MTCC 441), Aspergillus niger (MTCC 281), Trichoderma viridae (MTCC 167), Penicillium chrysogenum (MTCC 160), Fusarium moniliforme (MTCC 156) and Candida albicans (MTCC 183). Most of the compounds showed potent antibacterial and antifungal activity.

Synthesis and biological activity of pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one derivatives: in silico approach.

Xanthine oxidase (XO) is responsible for the pathological condition called gout. Inhibition of XO activity by various pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidine-4-one derivatives was assessed and compared with the standard inhibitor allopurinol. Out of 10 synthesized compounds, two compounds, viz. 3-amino-6-(2-hydroxyphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3b) and 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3g) were found to have promising XO inhibitory activity of the same order as allopurinol. Both compounds and allopurinol inhibited competitively with comparable Ki (3b: 3.56 microg, 3g: 2.337 microg, allopurinol: 1.816 microg) and IC(50) (3b: 4.228 microg, 3g: 3.1 microg, allopurinol: 2.9 microg) values. The enzyme-ligand interaction was studied by molecular docking using Autodock in BioMed Cache V. 6.1 software. The results revealed a significant dock score for 3b (-84.976 kcal/mol) and 3g (-90.921 kcal/mol) compared with allopurinol (-55.01 kcal/mol). The physiochemical properties and toxicity of the compounds were determined in silico using online computational tools. Overall, in vitro and in silico study revealed 3-amino-6-(4-chloro-2-hydroxy-5-methylphenyl)-1H-pyrazolo[3,4-d]thiazolo[3,2-a]pyrimidin-4-one (3g) as a potential lead compound for the design and development of XO inhibitors.

An improved procedure for synthesis of some new 1,3-diaryl-2-propen-1-ones using PEG-400 as a recyclable solvent and their antimicrobial evaluation.

A simple and convenient route is described for the synthesis of novel hetero 1,3-diaryl-2-propen-1-ones (chalcones) by using recyclable PEG-400 as an alternative reaction solvent. The reaction is clean with excellent yield, shorter reaction time and reduces the use of volatile organic compounds (VOCs). All the synthesized compounds were evaluated for their antimicrobial activities against several pathogenic representatives.