Competent synthesis of biaryl analogs via asymmetric Suzuki–Miyaura cross-coupling for the development of anti-inflammatory and analgesic agents

Based on the core structure of diflunisal drug, herein, we report a resembling series of biaryl analogs (3a–j) containing halogens, nitro, and methoxy substituents. They were designed and synthesized via a Suzuki–Miyaura cross-coupling reaction using Pd (OH)2 as a catalyst at a temperature of 65 °C with an intent to obtain improved and safer anti-inflammatory and analgesic agents. Suzuki–Miyaura transformation is the most significant among the cross-coupling reactions since its practical advantages include the commercially available low toxic reagents, mild reaction conditions, and functional group compatibility. On the other hand, a few conditions can be used to cross-couple aryl boronic acids or esters with aryl halides, especially 2-benzyl halides. Because of this, a novel Suzuki–Miyaura protocol is investigated that facilitates the selective conversion of halo aromatics, with an emphasis on the reaction to convert substituted bromobenzene to conjugated biphenyls. Finally, the obtained biaryl analogs (3a–j) were tested for in vitro and in vivo anti-inflammatory and analgesic applications. The results showed that compound 3b performed better than the standard drug with IC50 values comparable to that of the standard drug for COX-1 and COX-2 inhibition. Finally, molecular docking tests for the effective compound were carried out

Synthesis and evaluation of in vitro antimicrobial activity of novel 2-2-(aroyl)aroyloxymethyl-1,3,4-oxadiazoles

Synthetic pathway of the ten novel 2-2-(aroyl)aroyloxymethyl-1,3,4- oxadiazoles as new potential antimicrobial agents is illustrated. Intramolecular cyclization of 2-(2-aroylaryloxy) aceto hydrazides to 2-2-(aroyl)aroyloxy methyl-1,3,4-oxadiazoles was achieved with triethyl orthoformate in good yields. The compounds were characterized by IR, 1H NMR, mass spectra and by means of CHN analysis. The target compounds were tested for their in vitro antimicrobial activity against representative strains by disc diffusion method and micro dilution methods. Several compounds showed antimicrobial activity comparable with or higher than the standard drugs

Competent synthesis of biaryl analogs via asymmetric Suzuki-Miyaura cross-coupling for the development of anti-inflammatory and analgesic agents

Based on the core structure of diflunisal drug, herein, we report a resembling series of biaryl analogs (3a-j) containing halogens, nitro, and methoxy substituents. They were designed and synthesized via a Suzuki-Miyaura cross-coupling reaction using Pd (OH)(2) as a catalyst at a temperature of 65 degrees C with an intent to obtain improved and safer anti-inflammatory and analgesic agents. Suzuki-Miyaura transformation is the most significant among the cross-coupling reactions since its practical advantages include the commercially available low toxic reagents, mild reaction conditions, and functional group compatibility. On the other hand, a few conditions can be used to cross-couple aryl boronic acids or esters with aryl halides, especially 2-benzyl halides. Because of this, a novel Suzuki-Miyaura protocol is investigated that facilitates the selective conversion of halo aromatics, with an emphasis on the reaction to convert substituted bromobenzene to conjugated biphenyls. Finally, the obtained biaryl analogs (3a-j) were tested for in vitro and in vivo anti-inflammatory and analgesic applications. The results showed that compound 3b performed better than the standard drug with IC50 values comparable to that of the standard drug for COX-1 and COX-2 inhibition. Finally, molecular docking tests for the effective compound were carried out

Synchronization Algorithms and VLSI Implementation for DC-OFDM based UWB System

UWB is a promising technology for short-range high-rate wireless applicationa.It is able to providemaximal 480Mbps data-rate at a distance of 2 meters in realisticindoormulti-path environments. UWB technology is widely applied to the next generation WPAN as well as the wireless accessof consumer electronics at home. Recently, Multi-Band OFDM based UWB technology proposed by WiMedia has been selected as the international standard by ISO. In China, a new transmission architecture based on Dual-Carrier OFDM technology is adopted as UWB standard draft. Comparing to MB-OFDM based UWB system, DC-OFDM based UWB system has multiple advantages, like more spectrum resource,lower requirements on devices, etc. Besides, it is compatiblewith existing MB-OFDM based UWB technology. Therefore, DC-OFDM based UWB is more flexible. Synchronizationis the first step atthe receiver digital baseband, which is of tremendous importance in any wireless communication systems. The performance of synchronization directly determines whether the receiver can pick up radio signals correctly or not, whether the baseband modules can fulfill the digital signal processing effectively or not. The synchronization process in OFDM system can be briefly divided into two parts: symbol timing and frequency synchronization. Symbol timing serves to judge the starting position of OFDM symbolsafter considering the impact of multi-path fading channel.While the frequency synchronization estimates the multiple imperfections in analog front-end signal processing and make proper compensation. This thesis puts the emphasis on synchronization issues in DC-OFDM based UWB systems. We are the first to analyze the synchronization algorithm as well as the hardware implementation method tailored for DC-OFDM based UWB system. We also present the VLSI implementation result for synchronization module. The thesis consists of symbol timing and frequency synchronization. Regarding on the symbol timing, we analyze the impact of several synchronization errors inOFDM system. After that, we divide the synchronization process into four modulesby functionality: packet detection, coarse timing, TFC detection and fine timing. The internal parameters in each moduleare determined by system simulations. In the aspect of algorithm development, we adopt the joint auto-correlation and cross-correlation method to meet the requirements of UWB system in different indoor multi-path environments, and therefore achieve the robustness. In the aspect of hardware implementation, we put the attention on the structure of some key modules in symbol timing and their VLSI implementation result, such as auto-correlator, cross-correlator, real-number divider, etc. Regarding on the frequency synchronization, we first investigate the multiple analog front-end imperfections in OFDM system, like CFO, SFO and I/Q imbalance, and present their mathematics models respectively in DC-OFDM based UWB system.After that, we analyze the performance degradation in OFDM system due to these non-ideal effects by the metric of EVM. RF designer can build the connection between mismatching parameters and performance degradation by referring to the analysis. Hence, theRF designer is able to traceout the outline of system design. In the aspect of algorithm development, we explore the intrinsic character of I/Q imbalancewhich causes the image interference. Then, we design a set of new training sequences based on phase rotation and give the corresponding estimation algorithm.The simulation result shows that the new training sequence is able to obtain the diversity message introduced by I/Q imbalance and therefore achieve the diversity gain during demodulation process. In order to deal with the challenging situation where multiple analog front-end imperfections co-exist, we propose a joint estimation and compensation scheme. In the aspect of hardware implementation, we present the hardware structure of CFO estimation and compensation module catered for DC-OFDM based UWB system, with the emphasis on CORDIC unit that is responsible for triangle calculations. The VLSI implementation result shows that the proposed CFO estimation and compensation module satisfies the timing and resource requirements in DC-OFDM based UWB system. In the last, we present the prospective research area in 60-GHz applications. It includes multiplenon-ideal impairments, like phase noise, non-linear power amplification, DC offset, ADCs mismatch, etc. It is even more challenging to develop joint estimation and compensation scheme for these non-ideal effects

Synthesis of pyrimidones and evaluation of their xanthine oxidase inhibitory and antioxidant activities

The increasing prevalence of gout has been accompanied by a growing number of patients intolerant to or with disease refractory to the available urate-lowering therapies. This metabolic disease is a common disease with a higher prevalence in men older than 30 years and in women older than 50 years. These findings highlight the need for emerging treatments to effectively lower urate levels. In this view, we describe the xanthine oxidase (XO) inhibitory activities of the synthesized compounds 5a-j and also their antioxidant activities. Compounds 5c, 5d, 5f, 5h, and 5j exhibited good inhibitory activities against XO. On the other hand, compounds 5g and 5j exhibited moderate antioxidant activity. In order to find new urate-lowering compounds, the xanthine oxidase (XO) inhibitory and antioxidant activities of the newly synthesized pyrimidones 5a-j were evaluated. Compounds 5c, 5d, 5f, 5h, and 5j exhibited good inhibitory activities against XO. In addition, compounds 5g and 5j showed moderate antioxidant activity

Synthesis, characterization, and antibacterialactivity of 6-Chloro-8-methyl-2-oxo-2H-chromene-3-carboxylic acid ethyl ester

The title compound was synthesized by reacting 2-hydroxy-4-methoxy-benzaldehyde with diethyl malonate in the presence of piperidine cat-alyst and ethanol as solvent. The chemical structure of the title com-pound was elucidated by elemental analysis,1H-NMR, and IR. The crys-tal structure was determined by X-ray diffraction data. It crystallizes inmonoclinic crystal system, P21/c space group with unit cell parameters,a=12.840(2) ̊A, b=24.790(4) ̊A, c=7.8544(13) ̊A,β=98.035(5)°,V=2475.5(7) ̊A3,andZ=8. The molecular and crystal structure of the titlecompound is stabilized by inter- and intramolecular interactions of thetype C—H···O. The newly synthesized compound was screened for itsantibacterial activity against two gram-positive and two gram-negativebacteria

Synthesis and antiproliferative activity of benzophenone tagged pyridine analogues towards activation of caspase activated DNase mediated nuclear fragmentation in Dalton’s lymphoma

A series of benzophenones possessing pyridine nucleus 8a–l were synthesized by multistep reaction sequence and evaluated for antiproliferative activity against DLA cells by in vitro and in vivo studies. The results suggested that, compounds 8b with fluoro group and 8e with chloro substituent at the benzoyl ring of benzophenone scaffold as well as pyridine ring with hydroxy group exhibited significant activity. Further investigation in mouse model suggests that compounds 8b and 8e have the potency to activate caspase activated DNase (endonuclease) which is responsible for DNA fragmentation, a primary hallmark of apoptosis and thereby inhibits the Dalton’s lymphoma ascites tumour growth

Synthesis of novel morpholine conjugated benzophenone analogues and evaluation of antagonistic role against neoplastic development

A series of novel 4-benzyl-morpholine-2-carboxylic acid N′-2-(4-benzoyl-phenoxy)-acetyl-hydrazide derivatives 8a-j has been synthesized from (4-hydroxy-aryl)-aryl methanones through a multi-step reaction sequence and then evaluated for anti-proliferative activity in vitro against various types of neoplastic cells of mouse and human such as DLA, EAC, MCF-7 and A549 cells. From the cytotoxic studies and structural activity relationship of compounds 8a-j, it is clear that methyl group on the B ring of benzophenone is essential for antiproliferative activity and bromo at ortho position (compound 8b) and methyl at para position (compound 8f) on A ring of benzophenone are significant for extensive anti-mitogenic activity. Investigation on clonogenesis and Fluorescence-activated cell sorting suggests that compounds 8b and 8f have the potency to exhibit the prolonged activity with cell cycle arrest on G2/M phase against cancer progression. Further, the compounds 8b and 8f inhibit murine ascites lymphoma through caspase activated DNase mediated apoptosis

Synthesis and larvicidal properties of benzophenone comprise indole analogues against Culex quinquefasciatus

With the increase of resistance to conventionally used existing synthetic insecticides, vector management has become extremely challenging. Hence more attention has been focused on newly synthesized benzophenone integrated indole analogues. Therefore our present study was aimed to evaluate the efficacy of synthesized benzophenone integrated indoles against the larvae of filariasis vector mosquitoes, Culex quinquefasciatus employing standard WHO procedure at Mysore. Among all the synthesized compounds the efficacy of compounds 7a, 7b and 7j seemed to be efficient with LC50 values of 9.17, 3.93 and 1.63ppm respectively and LC90 values of 24.17, 8.85 and 6.17ppm respectively. From the results, compounds 7a, 7b and 7j seemed could be considered as powerful candidates to bring about useful synthetic insecticides so as to prevent the resurgence of mosquito vectors

DAO-9 (2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through caspase-3 mediated endonuclease activity in murine carcinoma

One of the main strategies to inhibit the tumor growth is to promote the biochemical events leading to DNA degradation, which would eventually culminate in apoptosis. We have earlier reported that the 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole(DAO-9) possessed anti-cancer activity. To address the exact molecular mechanism underlying anti-cancer property, present study focused on evaluating the anti-tumor effect of the DAO-9 on murine ascites carcinoma cells using various in vivo and in vitro assays. The in vivo assays implicated a strong regression in tumor growth of ascites carcinoma after treatment which is due to apoptogenic efficacy as assessed through structural morphology of EAC cells by Giemsa, Acridine orange, Annexin V staining and FACS analysis. Nucleosomal DNA fragmentation induced by DAO-9 is due to activation of caspase-3 mediated DNAse as verified by endonuclease assays and immunoblot analysis. The caspase-3 activation mechanism is by induction of intrinsic cascade signaling molecules, such as p53, Bax, Bad and cytochrome c (cyt c) expression as verified by western blot. The results concluded that the tumor inhibiting activity of DAO-9 is due to activation of the apoptotic signaling cascade, which could be translated into targeted anti-cancer drug in the near future