Synthesis and antiplasmodial evaluation of 1H-1,2,3-triazole grafted 4-aminoquinoline-benzoxaborole hybrids and benzoxaborole analogues.

A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids as well as aryl substituted benzoxaborole analogues was synthesized and screened for their anti-plasmodial efficacy against both chloroquine-susceptibility 3D7 and chloroquine-resistant W2 strains of P. falciparum. The inclusion of quinoline core among the synthesized analogues resulted in substantial enhancement of anti-plasmodial activities. Further, the spacer of a flexible alkyl chain is marginally preferred over piperazyl-ethyl in inhibiting growth of P. falciparum. The most potent 4-aminoquinoline-benzoxaborole conjugate with ethyl as spacer exhibited IC50 values of 4.15 and 3.78 µM against 3D7 CQ-susceptible and W2 CQ-resistant strains of P. falciparum with lower cross resistance with Chloroquine. There was no difference in anti-plasmodial activities between the CQ-susceptible 3D7 and CQ-resistant W2 strains of P. falciparum for the benzoxaborole derivatives lacking a quinoline core.

Target Classification in Synthetic Aperture Radar Images Using Quantized Wavelet Scattering Networks.

The need to classify targets and features in high-resolution imagery is of interest in applications such as detection of landmines in ground penetrating radar and tumors in medical ultrasound images. Convolutional neural networks (CNNs) trained using extensive datasets are being investigated recently. However, large CNNs and wavelet scattering networks (WSNs), which share similar properties, have extensive memory requirements and are not readily extendable to other datasets and architectures-and especially in the context of adaptive and online learning. In this paper, we quantitatively study several quantization schemes on WSNs designed for target classification using X-band synthetic aperture radar (SAR) data and investigate their robustness to low signal-to-noise ratio (SNR) levels. A detailed study was conducted on the tradeoffs involved between the various quantization schemes and the means of maximizing classification performance for each case. Thus, the WSN-based quantization studies performed in this investigation provide a good benchmark and important guidance for the design of quantized neural networks architectures for target classification.

1H-1,2,3-Triazole-tethered isatin-7-chloroquinoline and 3-hydroxy-indole-7-chloroquinoline conjugates: synthesis and antimalarial evaluation.

A series of 1H-1,2,3-triazole-tethered isatin-7-chloroquinoline and 3-hydroxy-indole-7-chloroquinoline conjugates have been synthesized and evaluated for their antimalarial activity against chloroquine-resistant W2 strain of Plasmodium falciparum. The most potent of the test compound with an optimum combination of 3-hydroxy-indole ring and a n-butyl linker displayed an IC50 value of 69 nM.

Synthesis and preliminary in vitro activity of mono- and bis-1H-1,2,3-triazole-tethered ß-lactam-isatin conjugates against the human protozoal pathogen Trichomonas vaginalis.

In this study, we describe the synthesis of mono- and bis-1H-1,2,3-triazole-tethered ß-lactam-isatin conjugates using copper-catalysed azide-alkyne cycloaddition reaction between mono- and di-propargylated azetidin-2-ones and N-alkylazido isatins. The synthesized conjugates were evaluated for their preliminary in vitro analysis against Trichomonas vaginalis at 50 µM. The efficacy of synthesized hybrids was observed to depend on the substituent at N-1 position of ß-lactam ring, as well as the presence of single/double 1H-1,2,3-triazole linker. Among the synthesized conjugates, the presence of a p-tolyl substituent at N-1 of ß-lactam ring was preferred for good activity profiles while the increase in spacer length did not influence the efficacy of the compounds. Compounds with high levels of potency were further analysed to determine their IC50 values, as well as cytotoxicity profiles against mammalian cells. The most active compound in the synthesized conjugates displayed an IC50 value of 10.49 µM against cultured G3 strain of T. vaginalis and was non-toxic to cultured mammalian HeLa cells at the same concentration.

Antiplasmodial and cytotoxicity evaluation of 3-functionalized 2-azetidinone derivatives.

3-Azido-, 3-amino- and 3-(1,2,3-triazol-1-yl)-ß-lactams were synthesized and evaluated for their antiplasmodial activity against four strains of Plasmodium falciparum and KB cells for their cytotoxicity profiles. The presence of a cyclohexyl substituent at N-1 and a phenyl group on the triazole ring markedly improved the activity profiles of triazole-tethered ß-lactam exhibiting IC(50) values of 1.13, 1.21 and 1.00 µM against 3D7, K1 and W2 strains respectively.

Amalgamating Isatin/Indole/Nitroimidazole with 7-chloroquinolines via azide-alkyne cycloaddition: Synthesis, anti-plasmodial, and cytotoxic evaluation.

The present paper describes the synthesis, anti-plasmodial, and cytotoxic evaluation of 7-chloroquinoline-based conjugates with isatins/indoles/ nitroimidazoles, obtained via Cu-promoted 1,3-dipolar cycloadditions. On contemplating SAR of the synthesized series, the inclusion of indole and nitroimidazole-core improved the anti-plasmodial activities while the isatin seemed to have a lesser effect. The conjugate with a nitroimidazole-core and hexyl chain length as a spacer between the two pharmacophores was found to be most potent among the synthesized series and displayed an IC50 of 0.12 µM and a selectivity index of 1748.

Triarylethylene-indolin-2,3-dione molecular conjugates: design, synthesis, docking studies and anti-proliferation evaluation.

A series of 1H-1,2,3-triazole-linked ospemifene-isatin and O-methylated ospemifene-isatin conjugates were synthesized and assayed for their anti-proliferative activities against estrogen-responsive as well as estrogen-non-responsive cells. The non-cytotoxic conjugate 14e, with an optimal combination of bromo substituents at the C-5/C-7 positions of isatin, proved to be a promising hit with an IC50 value of 31.62 µM against MCF-7 and 19.23 µM against MDA-MB-231. The observed anti-proliferative activities of active conjugates were further corroborated via docking studies carried out on estrogen receptor subtypes α and ß.

MICA: a multilinear ICA decomposition for natural scene modeling.

We refine the classical independent component analysis (ICA) decomposition using a multilinear expansion of the probability density function of the source statistics. In particular, we introduce a specific nonlinear system that allows us to elegantly capture the statistical dependences between the responses of the multilinear ICA (MICA) filters. The resulting multilinear probability density is analytically tractable and does not require Monte Carlo simulations to estimate the model parameters. We demonstrate the MICA model on natural image textures and envision that the new model will prove useful for analyzing nonstationarity natural images using natural scene statistics models.

Recent advances (2015-2016) in anticancer hybrids.

In spite of the development of a large number of novel anticancer drugs over the years, Cancer remains as a prominent cause of death, worldwide. Numerous drugs that are currently in clinical practice have developed multidrug resistance along with fatal side effects. Therefore, the utilization of single-target therapy is incapable of providing an effective control on the malignant process. Molecular hybridization, involving a combination of two or more pharmacophores of bioactive scaffolds to generate a single molecular architecture with improved affinity and activity, in comparison to their parent molecules, has emerged as a promising strategy in recent drug discovery research. Hybrid anticancer drugs are of great therapeutic interests since they can potentially overcome most of the pharmacokinetic drawbacks encountered with conventional anticancer drugs. Strategically, the design of anticancer drugs involved the blending or linking of an anticancer drug with another anticancer drug or a carrier molecule which can efficiently target cancer cells with improved biological potential. Major advantages of hybrid anticancer drugs involved increased specificity, better patient compliance, and lower side effects along with reduction in chemo-resistance. The successful utilization of this technique in design and synthesis of novel anticancer hybrids has been well illustrated and documented in the literature. The purpose of the present review article will be to provide an emphasis on the recent developments (2015-16) in anticancer hybrids with insights into their structure-activity relationship (SAR) and mechanism of action.

4-Aminoquinoline-chalcone/-N-acetylpyrazoline conjugates: Synthesis and antiplasmodial evaluation.

1H-1,2,3-triazole linked 4-aminoquinoline-chalcone/-N-acetylpyrazoline conjugates were synthesized and evaluated against cultured chloroquine (CQ) resistant strain. Antiplasmodial activities of the synthesized conjugates revealed dependence of activity on the length of the alkyl chain as well as on the presence of methoxy substituents on ring A/ring B of the chalcone. The most potent and non-cytotoxic conjugate showed comparable antiplasmodial activity with that of CQ, with an IC50 value of 53.7 nM.

Approximating filtered scale-variant signals.

We develop theorems that place limits on the point-wise approximation of the responses of filters, both linear shift invariant (LSI) and linear shift variant (LSV), to input signals and images that are LSV in the following sense: they can be expressed as the outputs of systems with LSV impulse responses, where the shift variance is with respect to the filter scale of a single-prototype fillter. The approximations take the form of LSI approximations to the responses. We develop tight bounds on the approximation errors expressed in terms of filter durations and derivative (Sobolev) norms. Finally, we find application of the developed theory to defoveation of images, deblurring of shift-variant blurs, and shift-variant edge detection.

Synthesis and in vitro antiplasmodial evaluation of 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone conjugates.

The manuscript describes the synthesis of novel amide tethered 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone bifunctional hybrids and their evaluation as antimalarial agents against W2 resistant strain of Plasmodium falciparum. The antiplasmodial activity of 7-chloroquinoline-ferrocenylchalcones was found to be less than their corresponding simple chalcone conjugates. The presence of a methoxy substituent at para position of ring B on chalcones and longer alkyl chain length markedly improved the antiplasmodial profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC50 value of 17.8 nM.

Urea/oxalamide tethered ß-lactam-7-chloroquinoline conjugates: synthesis and in vitro antimalarial evaluation.

The manuscript pertains to the synthesis of urea/oxalamide tethered ß-lactam-7-chloroquinoline conjugates with well modulated chain lengths and their antimalarial evaluation. The results reveal the dependence of activity profiles on the N-1 substituent of the ß-lactam ring, the nature of the linker as well as the length of the alkyl chain. The most potent of the tested compounds showed an IC50 of 34.97 nM against chloroquine resistant W2 strain of Plasmodium falciparum.

7-chloroquinoline-isatin conjugates: antimalarial, antitubercular, and cytotoxic evaluation.

A series of twenty piperazine-tethered 7-chloroquinoline-isatin hybrids have been synthesized via either direct nucleophilic substitution or Cu(Ι)Cl-mediated Mannich reaction. These new conjugates were evaluated for their antimalarial and antitubercular efficacy against a chloroquine-resistant strain of Plasmodium falciparum and Mycobacterium tuberculosis, respectively, while the cytotoxic profiles were evaluated against 3T6 cell line, a permanent mouse embryonic fibroblast cell line. The most potent of the test compound with IC50 of 0.22 µm against W2 strain of P. falciparum and 31.62 µm against the embryonic fibroblast cell line (cytotoxicity) displayed a high selective index of 143.73.

4-Aminoquinoline-ß-lactam conjugates: synthesis, antimalarial, and antitubercular evaluation.

A library of quinoline-ß-lactam-based hybrids was synthesized and tested for their antimalarial and antitubercular activities. The present antimalarial data showed the dependence of activity on the nature of linker, N-1 substituent of the ß-lactam ring as well as the length of alkyl chain. Most of the compounds are not as efficient as chloroquine in inhibiting the culture growth of Plasmodium falciparum W2 strain. Nevertheless, the synthesized hybrids showed better antitubercular activities (up to five times) compared with cephalexin (up to three times) and ethionamide.

Discovery of highly selective 7-chloroquinoline-thiohydantoins with potent antimalarial activity.

A series of C-3 thiourea functionalized ß-lactams, ß-lactam-7-chloroquinoline conjugates and 7-chloroquinoline-thiohydantoin derivatives were prepared with the aim of probing antimalarial structure-activity relationships. 7-Chlorquinoline-thiohydantoin derivatives were found to be potent inhibitors of cultured Plasmodium falciparum, with the most potent and non-cytotoxic compound exhibiting an IC50 of 39.8 nM. Studies of ß-hematin formation suggested that inhibition of haemozoin formation could be primary mechanism of action, with IC50 values comparable to those of chloroquine. Evaluation of cytotoxicity against HeLa cells demonstrated high selective indices.

Azide-alkyne cycloaddition en route to 1H-1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: synthesis and antimalarial evaluation.

We describe the synthesis and antimalarial activities of 1H-1,2,3-triazole tethered 7-chloroquinoline-isatin hybrids. Activity against cultured parasites was dependent on the C-5 substituent of the isatin ring as well as the alkyl chain length between the isatin and 7-chloroquinoline moieties. Compound 8h, with an optimum alkyl chain length (n = 3) and a chloro substituent at the C-5 position of the isatin ring, displayed the best activity among the test compounds, with IC50 value of 1.21 µM against cultured W2-strain Plasmodium falciparum.

Synthesis of 1H-1,2,3-triazole linked ß-lactam-isatin bi-functional hybrids and preliminary analysis of in vitro activity against the protozoal parasite Trichomonas vaginalis.

Twenty-two different triazoles were prepared to examine the anti-Trichomonas vaginalis structure-activity relationships (SAR) within the ß-lactam-isatin-triazole conjugate family. The compounds were synthesized by copper-catalyzed 'click chemistry.'In vitro activity against T. vaginalis was determined at 10 and 100 µM for each compound, with eighteen of the synthesized hybrids showing 100% growth inhibition at 100 µM. The compound 5i, with no cytotoxicity on cultured CHO-K1 cells, is considered a good compound for further analysis.

ß-Lactam synthon-interceded diastereoselective synthesis of functionalized octahydroindole-based molecular scaffolds and their in vitro cytotoxic evaluation.

A convenient and unprecedented synthesis of functionally enriched octahydroindole-based scaffolds has been developed via inter- and intra-molecular amidolysis of C-3 functionalized ß-lactams. The cytotoxic evaluation on oesophageal cancer cell line WHCO1 has revealed 7d as the most potent of the test compounds exhibiting an IC(50) value of 12.97 µM. The developed strategy further assumes significance as it entails the preparation of highly functionalized indoles without the aid of transition metal catalysis or pre-functionalization of substrates.

1,2,3-Triazole tethered ß-lactam-chalcone bifunctional hybrids: synthesis and anticancer evaluation.

The manuscript describes the synthesis of novel 1,2,3-triazole tethered ß-lactam-chalcone bifunctional hybrids via click chemistry approach utilizing azide-alkyne cycloaddition reactions and their evaluation as anticancer agents against four human cancer cell lines. The presence of a cyclohexyl substituent at N-1 of ß-lactam ring and methoxy substituents, preferably ortho on ring A and para on ring B on chalcones markedly improved the anticancer profiles of the synthesized scaffolds with the most potent of the test compound exhibiting an IC(50) value of <1, 67.1, <1 and 6.37 µM against A-549(lung), PC-3(prostate), THP-1(leukemia), and Caco-2(colon) cell lines, respectively.