Visible-light-induced C-S bond formation in the synthesis of 2,4-disubstituted thiazoles through cascade difunctionalization of acetophenone: a greener approach.

A groundbreaking approach has been developed for synthesizing 2,4-disubstituted thiazoles using an eco-friendly and metal-free approach. This novel method utilizes methyl aryl ketones, N-bromo-succinimide (NBS), and thioamides in water as a green reaction medium under visible light irradiation. Using NBS as a bromine source, the reaction takes place through an in situ α-bromination method. This approach does not require any catalyst, which makes it exceptionally beneficial for the environment. The advantages of this efficient approach are manifold and include the use of greener conditions, absence of metals, easy isolation of products, cost-effectiveness, non-toxicity, and reliance on renewable energy sources like visible light. Moreover, this technique offers higher product purity and excellent yield, enhancing itsappeal.

Microwave-assisted chemoselective transamidation of secondary amides by selective N-C(O) bond cleavage under catalyst, additive and solvent-free conditions.

A microwave-assisted, highly chemoselective protocol has been developed for the transamidation of tert-butyloxycarbonyl (Boc) activated secondary carboxamides with amines. Under non-conventional microwave techniques, the reactions were achieved under catalyst, additive, promoter and solvent-free conditions. The transamidation of a structurally diverse set of amides and amines was accomplished in good to excellent yields. The salient features of the developed methodology include a simple operation, broad substrate scope, functional group tolerance, practicality, and the scalability.

A green synthesis of pyrimido[4,5-b]quinolines and pyrido[2,3-d]pyrimidines via a mechanochemical approach.

A cost-effective and competent approach has been established for the synthesis of pyrimido[4,5-b]quinolines and pyrido[2,3-d]pyrimidines via a multicomponent reaction of 1,3 diketones (dimedone, barbituric acid, and Meldrum's acid), 6-aminouracil and aromatic aldehyde, through mechanochemical synthesis using a ball-mill. This transformation involves a one pot, catalyst-free, and solvent-free pathway to develop the desired products under mild reaction conditions.

Urea hydrogen peroxide-initiated synthesis of pyranopyrazoles through oxidative coupling under base- and metal-free conditions by physical grinding method.

A novel multicomponent one-pot expeditious synthesis of highly functionalized and pharmaceutically fascinated pyranopyrazoles has been developed. This reaction occurs via tandem Knoevenagel condensation reaction of methyl aryl derivatives, 3-methyl pyrazolone and malononitrile in the presence of urea hydrogen peroxide under the physical grinding method. The present methodology offers several benefits such as available green and cheap starting materials, solvent-free, mild reaction conditions, high atom economy, eco-friendly standards, excellent yields and easy isolation of the products without column chromatographic separation.

Eosin Y-Catalyzed Synthesis of 3-Aminoimidazo[1,2-a]Pyridines via the HAT Process under Visible Light through Formation of the C-N Bond.

A comfortable, environment-friendly, and metal-free approach for synthesizing the biologically important moiety aminoimidazopyridine through the multicomponent reaction of benzylamine, 2-aminopyridine, and t-butyl isocyanide under visible light using eosin Y as a photocatalyst has been developed. Inexpensive, nontoxic, the effortless accessibility of starting materials, and nonparticipation of particular glassware and a photoreactor system are important qualities of the current approach. Strangely, the mild conditions, environment-friendly, and enumerating tolerance of an extensive range of both electron-donating and electron-withdrawing groups are additional features of the approach.

Tetrahydropyrazolopyridines as antifriction and antiwear agents: experimental and DFT calculations.

Some tetrahydropyrazolopyridines (THPP-H) with the methoxy (THPP-OMe) and methyl (THPP-Me) substituents were synthesized by a one-pot multi-component reaction. NMR spectroscopy (1H and 13C) was used to authenticate the synthesis. According to the results of tribological tests ASTM D4172, and ASTM D5183 on a four-ball tester in paraffin oil (PO) at a concentration of 0.25% w/v, their relative tribo-activity along with a reference additive, zinc dialkyldithiophosphate (ZDDP) could be figured out as mentioned below-THPP-OMe > THPP-Me > THPP-H > ZDDP. The calculation of frictional power loss from the coefficient of friction data of the tested additives supports the given order. As is apparent from AFM and SEM micrographs of the wear scar surface for plain oil with and without different tetrahydropyrazopyridines, surface evenness endorses the above trend. Proof for strong adsorption of the synthesized additives is provided by EDX analysis of the steel ball surface after performing the tribological test, where nitrogen and oxygen are vividly seen as heteroatoms. XPS studies reveal the composition of the in situ formed tribofilm. The moieties containing carbon bonded to oxygen/nitrogen as decomposed products of the additive together with oxides of iron in +II or +III oxidation states are perceptible in the tribofilm, the tribofilm interferes with the proximity of the surfaces keeping them far apart. Consequently, friction and wear are remarkably reduced. Findings from Density Functional Theory (DFT) calculations are in full agreement with the results obtained from tribological experiments.

Lemon juice catalyzed C-C bond formation via C-H activation of methylarene: a sustainable synthesis of chromenopyrimidines.

An economical and proficient approach has been developed for the synthesis of chromenopyrimidines via three-component reaction of thiobarbituric acid/barbituric acid, methylarenes and dimedone/1,3-cyclohexanedione by using lemon juice as a natural, biodegradable catalyst and TBHP as an oxidant. This transformation involves metal-free C-C bond formation via C-H activation of methylarenes under mild reaction conditions.

Chitosan: A macromolecule as green corrosion inhibitor for mild steel in sulfamic acid useful for sugar industry.

The present investigation aims at investigation of low cost nontoxic carbohydrate biopolymer chitosan as corrosion inhibitor alone and in combination with KI for mild steel in 1M sulfamic acid medium using gravimetric, electrochemical and surface analysis techniques. It is found that chitosan alone exhibits inhibition efficiency of 73.8% at 200ppm concentration. However, in combination with KI (5ppm), it gave more than 90% inhibition efficiency. The significant increase in the inhibition performance of chitosan has been explained by the synergistic mechanism. The results of Potentiodynamic polarization study shows that chitosan and its blend with KI decreases both anodic and cathodic reactions occurring at mild steel surface in 1M sulfamic acid medium by blocking active sites of the metal and acts as mixed type inhibitor. EIS study reveals that the polarization resistance increases with increase in the concentration of inhibitors which increases charge transfer resistance across the metal/solution interface. The adsorption of chitosan followed the Langmuir adsorption isotherm. The formation of inhibitor film on metal surface was supported by scanning electron microscopy (SEM) and atomic force microscopy (AFM) surface studies.

Microwave-Induced Synthesis of Chitosan Schiff Bases and Their Application as Novel and Green Corrosion Inhibitors: Experimental and Theoretical Approach.

Environmentally friendly three chitosan Schiff bases (CSBs) were first time synthesized under microwave irradiation by the reaction of chitosan and aldehydes [benzaldehyde (CSB-1), 4-(dimethylamino)benzaldehyde (CSB-2), and 4-hydroxy-3-methoxybenzaldehyde (CSB-3)] and characterized by IR and NMR spectroscopy. The corrosion inhibition performance of the synthesized inhibitors was studied by the electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP). The results show that all the Schiff bases (CSBs) act as effective corrosion inhibitors for mild steel in 1 M HCl solution. Among the synthesized Schiff bases, CSB-3 exhibited the maximum inhibition efficiency of 90.65% at a very low concentration of 50 ppm. The EIS results showed that the CSBs inhibit corrosion by the adsorption mechanism. The PDP results show that all the three Schiff bases are mixed-type inhibitors. The formation of inhibitor films on the mild steel surface was supported by scanning electron microscopy/energy dispersive X-ray analysis and Fourier-transform infrared spectroscopy methods. The adsorption of CSBs on the mild steel surface obeys the Langmuir adsorption isotherm. The theoretical studies via density functional theory and molecular dynamics simulation corroborated the experimental results.

Stephanine from Stephania venosa (Blume) Spreng Showed Effective Antiplasmodial and Anticancer Activities, the Latter by Inducing Apoptosis through the Reverse of Mitotic Exit.

Extracts from the tubers of Stephania venosa (Blum) Spreng growing in Vietnam significantly inhibited cell proliferation against a number of cancer cells including HeLa, MDA-MB231 and MCF-7 cells. A bioassay-guided fractionation led to the isolation of four aporphine and one tetrahydroprotoberberine alkaloids: dehydrocrebanine 1, tetrahydropalmatine 2, stephanine 3, crebanine 4 and O-methylbulbocapnine 5. The characterization of these compounds was based on MS, NMR and published data. A study by structure-bioactivity relationship on these isolates showed that stephanine is the most active compound. Cell biological studies showed that stephanine induces the reverse of mitotic exit, eventually leading to cell death by apoptosis. This data suggests that stephanine has a unique mode of cell-killing activity against cancer cells, which is seldom observed with known synthetic compounds. In addition to its anticancer property, our data from an in vitro study showed that S. venosa also possesses effective antiplasmodial activity and stephanine was also the most interesting compound but is the most cytotoxic with the lowest selectivity index. Copyright © 2017 Her Majesty the Queen in Right of Canada Phytotherapy Research StartCopTextCopyright © 2017 John Wiley & Sons, Ltd.

In silico CD4+, CD8+ T-cell and B-cell immunity associated immunogenic epitope prediction and HLA distribution analysis of Zika virus.

Zika virus (ZIKV) is a mosquito-borne flavivirus distributed all over Africa, South America and Asia. The infection with the virus may cause acute febrile sickness that clinically resembles dengue fever, yet there is no vaccine, no satisfactory treatment, and no means of evaluating the risk of the disease or prognosis in the infected people. In the present study, the efficacy of the host's immune response in reducing the risk of infectious diseases was taken into account to carry out immuno-informatics driven epitope screening strategy of vaccine candidates against ZIKV. In this study, HLA distribution analysis was done to ensure the coverage of the vast majority of the population. Systematic screening of effective dominant immunogens was done with the help of Immune Epitope & ABCPred databases. The outcomes suggested that the predicted epitopes may be protective immunogens with highly conserved sequences and bear potential to induce both protective neutralizing antibodies, T & B cell responses. A total of 25 CD4+ and 16 CD8+ peptides were screened for T-cell mediated immunity. The predicted epitope "TGLDFSDLYYLTMNNKHWLV" was selected as a highly immunogenic epitope for humoral immunity. These peptides were further screened as non-toxic, immunogenic and non-mutated residues of envelop viral protein. The predicted epitope could work as suitable candidate(s) for peptide based vaccine development. Further, experimental validation of these epitopes is warranted to ensure the potential of B- and T-cells stimulation for their efficient use as vaccine candidates, and as diagnostic agents against ZIKV.

Synthesis and bio-evaluation of novel quinolino-stilbene derivatives as potential anticancer agents.

A series of 25 novel quinolino-stilbene derivatives were designed, synthesized and evaluated for their potential as anticancer agents. Three of them not only displayed quite potent antiproliferative activity with IC50 values<4µM but also showed approximately twofold selectivity against cancer cells, compared to non-cancerous cells. Three other compounds exhibited comparatively good activity with IC50 values in the range of 4-10µM, and the rest was moderately active or inactive. One of these viz. 3-[E-(4-fluorostyryl)]-2-chloroquinoline (compound 7B) caused substantial DNA damage and arrested cell cycle in S phase. Interestingly, 7B was very active against MDA-MB468 (IC50=0.12µM), but not against other cell lines examined. Compound 3-[Z-(3-(trifluoromethyl)styryl)]-2-chloroquinoline (12A), the most effective against all cancer cell lines examined, caused prolonged cell cycle arrest at mitosis and eventually apoptosis. Data from an in vitro study showed that compound 12A inhibited microtubule polymerization in a similar fashion to nocodazole. Further study using in silico molecular modeling revealed that 12A causes the impediment of microtubule polymerization by binding to tubulin at the same cavity where podophyllotoxin binds.

A Novel Approach for Overcoming Drug Resistance in Breast Cancer Chemotherapy by Targeting new Synthetic Curcumin Analogues Against Aldehyde Dehydrogenase 1 (ALDH1A1) and Glycogen Synthase Kinase-3 ß (GSK-3ß).

Breast cancer stem cells are well known to resist the traditional methods like chemo and radio therapy. Aldehyde dehydrogenase 1 (ALDHIA1) and glycogen synthase kinase-3 ß (GSK-3ß) are the two selected proteins for study, due to their overexpression and upregulation in breast cancer cells. Curcumin, the yellow pigment of the spice turmeric, is widely reported as an antioxidant and acts as a synergist along with traditional drugs. Under hypoxic conditions, it gets converted to free radical which causes apoptosis. Three naturally occurring curcuminoids, i.e. curcumin, demethoxycurcumin, and bisdemethoxycurcumin along with five derivatives/analogues of curcumin, viz. 4,4'-di-O-(carboxy-methyl)-curcumin, 4-O-(2-hydroxyethyl)curcumin, 4,4'-di-O-allyl-curcumin, 4,4'-di-O-(acetyl)-curcumin, and 3,3'-bisdemethylcurcumin were synthesized and evaluated for their anti-breast cancer potential by docking simulation and assessment of their antioxidant character, studied via 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(·+)) radical cation scavenging assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical, and ferric reducing ability potential (FRAP) assay. A co-relation between structure and activity of curcuminoids/its analogues and derivatives has been worked out.

Interaction pattern for the complex of B-DNA Fullerene compounds with a set of known replication proteins using docking study.

Fullerenes have attracted considerable attention due to their unique chemical structure and potential applications which has opened wide venues for possible human exposure to various fullerene types. Therefore, in depth knowledge of how fullerene may interfere with various cellular processes becomes quite imperative. The present study was designed to investigate how the presence of fullerene affect the binding of DNA with different enzymes involved in replication process. Different fullerenes were first docked with DNA and then binding scores of different enzymes was analyzed with fullerene docked DNA. C30, C40 & C50 once docked with DNA, reduced the binding score of primase, whereas no significant change in the binding score was observed with the helicase, ssb protein, dna pol δ, dna pol ε, ligase, DNA clamp, and topoisomerases. On the contrast, the binding score of RPA14 decreases in fluctuating manner while interacting with increasing molecular weight of fullerene bound single-stranded DNA complex. The study revealed the affect of fullerene family interacting with DNA on the binding pattern of enzymes involved in replication process. Study suggests that the presence of most of fullerenes may not affect the activity of these enzymes necessary for replication process whereas C30, C40 & C50 may disrupt the activity of primase, (strating point for DNA polymerase) its docking score decreases from 13820 to 10702.

Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents.

Chloroquine (CQ) has a broad spectrum of pharmacological activities including anticancer and anti-inflammatory, in addition to its well-known antimalarial activity. This very useful property of CQ may be rendered through a variety of different molecular and cellular mechanisms, including the induction of apoptosis, necrosis and lysosomal dysfunction. CQ alone may not be as effective as many well-known anticancer drugs; however, it often shows synergisticts when combined with other anticancer agents, without causing substantial ill-effects. To increase its pharmacological activity, scientists synthesized many different chloroquine derivatives by a repositioning approach, some of which show higher activities than the parental CQ. To further improve anticancer activity, medicinal chemists have recently been focusing on generating CQ hybrid molecules by joining, directly or through a linker, 4-aminoquinoline and other pharmacologically active phamarcophore(s). Indeed, some CQ hybrid molecules substantially improved anticancer activity while maintaining desirable CQ property, providing an excellent opportunity of developing effective and safe novel anticancer agents. Since the approach of developing CQ hybrid molecules has advanced much more in the antimalarial drug research, it can provide an excellent template for anticancer drug development. This review provides an overview of CQ-based hybrid molecules by focusing on: (1) the potential advantage of the hybrid approach in developing effective and safe anticancer agents; (2) what we can learn from the CQ hybrid approach used in the development of effective antimalarial agents; and (3) CQ hybrid molecules as potential anticancer agents in different categories classified based on their chemical compositions.

INTERACTION PATTERN OF FULLERENES (C20-C180) AND CARBON NANOTUBES WITH DIFFERENT FORMS OF DNA: A COMPUTATIONAL BIOLOGY APPROACH.

Recently, the venues of exposure to nanoparticles have increased significantly owing to their increased deliberate production. In this study the interaction of fullerenes with DNA was analyzed along with various factors affecting this interaction like mol. wt. of fullerenes (C20 to C180), the form of DNA i.e., A, B and Z, and sequences of DNA, and was compared with the DNA binding of CNTs. Increase in the molecular weight of the fullerene showed increase in the binding score with A & B-form of DNA, but no regular affect was seen on binding with Z-form of DNA. Although the binding of all fullerenes was best with A form. While CNTs bind with all forms of DNA, but best scores were with B form, which were comparable with those of fullerene C80 and C84 with A form. The interaction of both fullerenes and CNTs were not affected by the sequence of DNA. The number of interacting base pairs increased from 1 base-pair to 4, as the molecular size of fullerene increases in all A & B-and Z form of DNA. Whereas CNTs interact with 5 bases in A and B form, and 3 bases in Z form. The groove where binding occurs depended on the form of DNA. Smaller (< C48) fullerenes bind in minor groove of B-DNA, and larger fullerenes bind in major groove. While in A form of DNA, fullerenes of all sizes bind in major groove. The binding was random and not size dependent in Z form of DNA. Whereas, CNTs bind to major groove of DNA in a parallel fashion in A and B form of DNA, and in minor groove attached perpendicularly in Z form.

Synthesis and in vivo evaluation of 11-substituted estradiol derivatives as anti-implantation agents.

Synthesis of 11-substituted estradiol derivatives (12-17) has been carried out by the Grignard reaction with alkyl, allyl, and benzyl halides on 17beta-hydroxy-3-methoxy-11-oxo-estra-1,3,5(10),8(9)-tetraene (10). The novel compounds (10 and 12-17) were evaluated for their preliminary post-coital contraceptive (anti-implantation) activity in Sprague-Dawley rats. The tested compounds were administered orally and showed significant anti-implantation activity. Compound 13 is the most potent compound in the series which showed 100% contraceptive efficacy at 1.25 mg kg(-1).

Separation and quantification of lignans in Phyllanthus species by a simple chiral densitometric method.

A sensitive, selective, and robust high-performance TLC (HPTLC) method using chiral TLC plates for qualitative and quantitative analysis of phyllanthin (A), hypophyllanthin (B), niranthin (C), and nirtetralin (D), the active lignans of Phyllanthus species, was developed and validated. The effectiveness and role of various stationary phases viz TLC silica gel 60F(254), HPTLC silica gel 60F(254), and chiral TLC plates in the quantitation were evaluated. A precoated chiral TLC plate was found suitable for the simultaneous analysis of four pharmacologically active lignans. For achieving good separation, the optimized mobile phase of n-hexane/acetone/1,4-dioxane (9:1:0.5 by volume) was used (R(f) = 0.30, 0.36, 0.41, and 0.48 for compounds A, B, C, and D, respectively). A densitometric determination of the above compounds was carried out in reflection/absorption mode at 620 nm. Optimized chromatographic conditions provide well-separated compact bands for the tested lignans. The calibration curves were found linear in the concentration range of 100-500 ng/band. Recoveries of A-D were 99.98, 100.51, 99.22, and 98.74%, respectively. The method was validated according to ICH guidelines. The method reported here is reproducible and applied for the quantitative analysis of the above lignans in the leaves of four Phyllanthus species, i. e., P. amarus, P. maderaspatensis, P. urinaria, and P. virgatus.

Synthesis of diverse analogues of Oenostacin and their antibacterial activities.

Several diverse analogues of Oenostacin, a naturally occurring potent antibacterial phenolic acid derivative, have been synthesized. A small library with more than forty analogues having different aromatic rings and varied side chains has been achieved through solution phase synthesis. Some of these analogues, that is, 22, 23 and 42, possessed potent antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus having EC(50) ranging from 0.49 to 0.67 microM as compared to Oenostacin (EC(50)=0.12 microM).

Synthesis of gallic acid based naphthophenone fatty acid amides as cathepsin D inhibitors.

Gallic acid, one of the most abundant plant phenolic acids, has been modified to cathepsin D protease inhibitors. The strategy of modification was proposed basing on some previously reported structure and activity relationship (SAR) studies. The synthesized naphthophenone fatty acid amide derivatives have been evaluated for in vitro cathepsin D inhibition activity. Two of them have shown significant inhibition activity with IC(50) values of 0.06 and 0.14 microM, respectively, as compared against pepstatin (0.0023 microM), the most potent inhibitor known so far. The study revealed that such attempts on gallic acid based pharmacophores might result in potent inhibitors of cathepsin D.