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We develop an extended Kalman filter-based vehicle tracking algorithm, specifically designed for uniform planar array layouts and vehicle platoon scenarios. We first propose an antenna placement strategy to design the optimal antenna array configuration for precise vehicle tracking in vehicle-to-infrastructure networks. Furthermore, a vehicle tracking algorithm is proposed to improve the position estimation performance by specifically considering the characteristics of the state evolution model for vehicles in the platoon. The proposed algorithm enables the sharing of corrected error transition vectors among platoon vehicles, for the purpose of enhancing the tracking performance for vehicles in unfavorable positions. Lastly, we propose an array partitioning algorithm that effectively divides the entire antenna array into sub-arrays for vehicles in the platoon, aiming to maximize the average tracking performance. Numerical studies verify that the proposed tracking and array partitioning algorithms improve the position estimation performance. [ABSTRACT FROM AUTHOR]

Millimeter-wave vehicle-to-vehicle communication systems with multiple-input multiple-output antenna array have drawn significant attention because it is expected to satisfy the growing bandwidth requirements for the cooperative intelligent transportation systems. However, maintaining high-quality communication links between communicating vehicles without high overhead is a challenging problem due to the high mobility of vehicles. In this paper, we propose a beam management algorithm with spatially distributed antenna subarrays instead of a single co-located antenna array. Unlike existing methods, we use distributed antenna subarrays to exploit the geometric relationship of the beam directions and the relative distance between communicating vehicles. We reduce the beam alignment errors by minimizing the sum of squared errors between the estimated beam direction after the beam training process and the refined beam direction derived from the measured position and velocity data. Additionally, a position data request protocol is devised to reduce the beam refining errors. Numerical results demonstrate that the proposed beam management algorithm successfully reduces the beam alignment errors and it is robust to position and velocity measurement errors. [ABSTRACT FROM AUTHOR]

We consider a reflection pattern (RP) designfor reconfigurable intelligent surface (RIS)-assisted vehicle-to-vehicle (V2V) communication systems. Fast-moving-vehicle environments necessitate developing more intuitive RP alignment technique that aligns a predefined codeword to the dominant channel directions. To support a fast RP alignment in RIS-assisted V2V systems, we provide a design guideline of the RP codebook by considering passive reflecting elements at the RIS. We analyze distributions of the incident and reflection channels by taking the street geometry in V2V networks into consideration. By using the statistical information on the difference in spatial frequencies between the incident and reflection channels, we define a set of ideal RPs that are likely to maximize a reflection beamforming gain. The RP codebook is constructed by designing a set of reflecting codewords that can generate actual RPs close to predefined ideal RPs. Numerical results verify that the proposed RP codebook provides a higher link gain than previously reported codebooks. [ABSTRACT FROM AUTHOR]

We develop joint vehicle tracking and road side unit (RSU) selection algorithms suitable for vehicle-to-infrastructure (V2I) communications. We first design an analytical framework for evaluating vehicle tracking systems based on the extended Kalman filter. A simple, yet effective, metric that quantifies the vehicle tracking performance is derived in terms of the angular derivative of a dominant spatial frequency. Second, an RSU selection algorithm is proposed to select a proper RSU that enhances the vehicle tracking performance. A joint vehicle tracking algorithm is also developed to maximize the tracking performance by considering sounding samples at multiple RSUs while minimizing the amount of sample exchange. The numerical results verify that the proposed vehicle tracking algorithms give better performance than conventional signal-to-noise ratio-based tracking systems. [ABSTRACT FROM AUTHOR]

Vehicle-to-everything communication system is a strong candidate for improving the driving experience and automotive safety by linking vehicles to wireless networks. To take advantage of the full benefits of vehicle connectivity, it is essential to ensure a stable network connection between roadside unit (RSU) and fast-moving vehicles. Based on the extended Kalman filter (EKF), we develop a vehicle tracking algorithm to enable reliable radio connections. For the vehicle tracking algorithm, we focus on estimating the rapid changes in the beam direction of a high-mobility vehicle while reducing the feedback overhead. Furthermore, we design a beamforming codebook that considers the road layout and RSU. By leveraging the proposed beamforming codebook, vehicles on the road can expect a service quality similar to that of conventional cellular services. Finally, a beamformer selection algorithm is developed to secure sufficient gain for the system's link budget. Numerical results verify that the EKF-based vehicle tracking algorithm and the proposed beamforming structure are more suitable for vehicle-to-infrastructure networks compared to existing schemes. [ABSTRACT FROM AUTHOR]

We develop a channel-adapted multiuser transmission algorithm for millimeter wave (mmWave) wireless systems. We first study the impact of multiuser diversity on the beam alignment performance of mmWave systems. Assuming a multiuser framework, we derive the probability of beam misalignment as a function of the number of users. Moreover, we estimate the achievable sum-rate of multiuser systems relying upon beam alignment. We develop an adaptive transmission algorithm that changes the number of scheduled users according to channel conditions. Simulation results verify that the proposed algorithm provides better sum-rate performances than previous systems. [ABSTRACT FROM AUTHOR]

• High-speed (~5 mm·s−1) continuous solution-shearing method was introduced to fabricate the large grained (>100 μm) perovskite thin films and their photovoltaic devices. • Only 3.5 μL of perovskite precursor solution was consumed for 4.25 cm2 film so that this shearing deposition is more environmentally eco-friendly approach compared to the spin-coating. • The hydrophobic top plate enables to deposit more densely packed films with less void formation, consequently leading to the improved photovoltaic performance. High-speed continuous deposition of solution-processed perovskite thin films with controlled microstructural morphology has been intensively pursued toward practical commercialization of high-efficiency perovskite solar cells. In order to meet this urgent demand in a timely manner, we present a rapid (~5 mm·s−1) scalable meniscus-controlled coating method to deposit large-grained (>100 μm) perovskite thin films over large area. Shearing movement of the meniscus of perovskite solution, confined by the hydrophobic-treated top and temperature-controlled bottom plates enables a rapid crystallization of perovskite grains, also facilitating the continuous influx of solutes at the meniscus for continuous film growth with less consumption of perovskite solution. Optical and structural analyses revealed that the rapid-shear-deposited perovskite thin films possess a large-grained, densely-packed and highly-crystalline phase. Consequently, perovskite solar cell based this film exhibits the power conversion efficiency of 10.9% even without compositional engineering and additive controls. Therefore, it can be claimed that this rapid shearing deposition of perovskite solution paves a way to achieve a cost-competitive production of the high-efficiency solar cell. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Discovery of mutant-selective kinase inhibitors is one of the challenges in medicinal chemistry and is a main issue for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. We tried to improve the selectivity of pan-HER inhibitors for mutant EGFRs. Utilizing click chemistry, triazole-tethered quinazoline derivatives were synthesized, based on a quinazoline scaffold showing pan-HER inhibition. The representative compound 5j exhibited 17- and 52-fold improved selectivity for EGFR L858R/T790M over wild-type EGFR and HER2, respectively, and demonstrated 6.7-fold more potent antiproliferative activity against PC9 cells harboring EGFR-activating mutation than gefitinib. Although the described quinazolines did not surpass pyrimidines as 3rd generation EGFR inhibitors in terms of selectivity for mutant EGFRs, our approach might provide information that would help in the identification of mutant-selective compounds among pan-HER inhibitors using the quinazoline scaffold. [ABSTRACT FROM AUTHOR]

In this paper, we exploit the concept of array pattern synthesis to design cluster beamformers with partial channel state information for non-orthogonal multiple access downlink multiuser transmission in millimeter wave channels. Using the information on angle-of-departure region for each user, we formulate an array pattern nulling problem to design each cluster beamformer for minimizing inter-cluster interferences, which is solved by using semidefinite programing. Further, we exploit linear programing to solve a power allocation problem for each user in the cluster to achieve a target signal-to-interference-and-noise ratio. Numerical results are presented to verify the validity of the proposed schemes. [ABSTRACT FROM AUTHOR]

In view of the few reports concerning aromatic nucleophilic substitution reactions featuring an alkoxy group as a leaving group, the aromatic nucleophilic substitution of 2,4-dimethoxynitrobenzene was investigated with a bulky t-butoxide nucleophile under microwave irradiation. The transetherification of 2,4-dimethoxynitrobenezene with sodium t-butoxide under specific conditions, namely for 20 min at 110°C in 10% dimethoxyethane in toluene, afforded the desired product in 87% yield with exclusive ortho-selectivity. A variety of reaction conditions were screened to obtain the maximum yield. The aromatic nucleophilic substitution of 2,4-dimethoxynitrobenzene with t-butoxide should be carried out under controlled conditions in order to avoid the formation of byproducts, unlike that of dihalogenated activated benzenes. Among the formed byproducts, a major compound was elucidated as 2,4-dimethoxy-N-(5-methoxy-2-nitrophenyl)aniline by X-ray crystallography. [ABSTRACT FROM AUTHOR]

The discovery of small-molecule regulators of microRNAs remains challenging, but a few have been reported. Herein, we describe small-molecule inhibitors of miR-31, a tumor-associated microRNA (miRNA), identified by high-throughput screening using a cell-based reporter assay. Aminosulfonylarylisoxazole compounds exhibited higher specificity for miR-31 than for six other miRNAs, i.e., miR-15a, miR-16, miR-21, miR-92a-1, miR-146a, and miR-155, and increased the expression of miR-31 target genes. The down-regulation of mature miR-31 was observed, while its precursor form increased following treatment with the compounds. Thus, the compounds may target the processing of pre-miR-31 into mature miR-31 and thereby inhibit the production of mature miR-31. [ABSTRACT FROM AUTHOR]

Fifth generation wireless networks are expected to utilize wide bandwidths available at millimeter wave (mmWave) frequencies for enhancing system throughput. However, the unfavorable channel conditions of mmWave links, such as, higher path loss and attenuation due to atmospheric gases or water vapor, hinder reliable communications. To compensate for these severe losses, it is essential to have a multitude of antennas to generate sharp and strong beams for directional transmission. In this paper, we consider mmWave systems using uniform planar array (UPA) antennas, which effectively place more antennas on a 2-D grid. A hybrid beamforming setup is also considered to generate beams by combining a multitude of antennas using only a few radio frequency chains. We focus on designing a set of transmit beamformers generating beams adapted to the directional characteristics of mmWave links assuming a UPA and hybrid beamforming. We first define ideal beam patterns for UPA structures. Each beamformer is constructed to minimize the mean squared error from the corresponding ideal beam pattern. Simulation results verify that the proposed codebooks enhance beamforming reliability and data rate in mmWave systems. [ABSTRACT FROM PUBLISHER]

Antiangiogenic agents have been widely investigated in combination with standard chemotherapy or targeted cancer agents for better management of advanced cancers. Therapeutic agents that concurrently inhibit epidermal growth factor receptor and other angiokinases could be useful alternatives to combination therapies for epidermal growth factor receptor-dependent cancers. Here, we report the synthesis of an indole derivative of pazopanib using a bioisosteric replacement strategy, which was designated MKP101. MKP101 inhibited not only the epidermal growth factor receptor with an IC50 value of 43 nM but also inhibited angiokinases as potently as pazopanib. In addition, MKP101 effectively inhibited vascular endothelial growth factor-induced endothelial proliferation, tube formation, migration of human umbilical vein endothelial cells and proliferation of HCC827, an epidermal growth factor receptor-addicted cancer cell line. A docking model of MKP101 and the kinase domain of the epidermal growth factor receptor was generated to predict its binding mode, and validated by synthesizing and evaluating MKP101 derivatives. Additionally, a study of structure-activity relationships of indolylamino or indolyloxy pyrimidine analogues derived from MKP101 demonstrated that selectivity for epidermal growth factor receptor and other angiokinases, especially vascular endothelial growth factor receptor 2 depends on the position of substituents on pyrimidine and the type of link between pyrimidine and the indole moiety. We believe that this study could provide a basis for developing angiokinase inhibitors having high affinity for the epidermal growth factor receptor, from the pyrimidine scaffold. [ABSTRACT FROM AUTHOR]

Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis . We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement. [ABSTRACT FROM AUTHOR]

The article discusses the synthesis and biological evaluation of biarylamide derivatives that are inhibitors of phagocytosis in macrophages. Topics include the immune cells macrophages which are important innate immune system, the phagocytosis process that involves a number of biomolecules such as cell surface receptors and cytoskeletal proteins and the use of potent small molecules against phagocytosis for exploring structure-activity relationship (SAR) of the biaryl amide compounds.

Geckos exhibit a unique ability to adhere repeatedly and reversibly to a variety of surfaces. Considerable scientific and engineering efforts over the last decade have produced gecko-inspired adhesives which can outperform the gecko in some regards. However, the best results come from adhesives which are difficult to mass-produce, or degrade through repeated use. Here, we propose a method for fabricating micrometer-scale, gecko-inspired adhesive structures with mushroom tips in densely packed arrays using deep reactive ion etching (DRIE) and soft mold replication. We use xenon difluoride etching to release the cured polymer structures from the DRIE-processed silicon wafer, and soft mold replication to avoid surface fluorination in the final adhesive patches. The patterned adhesives exhibit more than an order of magnitude increase in pull-off force compared to an unstructured, flat control sample. More importantly, the adhesives’ structures retain 80% of their original attachment strength through repeated use, even after 1000 contact cycles. To investigate the importance of three parameters described in theoretical works, we characterize the effect of boundary conditions on friction, the effect of backing layer on pull-off force, and the effect of retraction speed on pull-off force. Our fabrication approach could be used to mass produce wafer-size patches of structured adhesive that exhibit higher repeatability and the utilized experimental adhesive characterization methods will allow better optimization of future gecko-inspired adhesive designs. [ABSTRACT FROM PUBLISHER]

Abstract: 5,6,7,8-Tetrahydro-4H-cyclohepta[d]isoxazole derivatives were synthesized and evaluated as a novel class of inhibitors for α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis in a mouse melanoma B16F10 cell line. Compound 8e (IC50 =0.67μM), 8h (IC50 =1.01μM) and 9b (IC50 =0.99μM) exhibited a potent inhibitory activity approximately 85- to 126-fold greater than kojic acid, a well-known potent inhibitor. A biochemical study indicates that the activity of this series should be displayed via down-regulation of the expression of tyrosinase. [Copyright &y& Elsevier]

To understand whether imidazothiazoles inhibit NF- B mediated signaling, we carried out an image-based assay visualizing translocation of NF- B by using an immunofluorescent staining method.[9] Immunostaining was performed after the short-time exposure of chemicals. In summary, we found novel NF- B inhibitors through a phenotype-based assay and immunocytochemistry for translocation of NF-kB. NF- B, Imidazothiazole, Nitric oxide, Small molecule inhibitor. [Extracted from the article]

The safety and consistency of platoon-based driving are guaranteed via reliable communication between vehicles in a platoon. In this paper, we propose to exploit a full-duplex (FD) relay vehicle for millimeter-wave vehicular communications in platoon-based driving. Considering that a lead vehicle broadcasts information to all vehicles in a platoon, we consider two power allocation problems—maximizing broadcast information rates with a power constraint and minimizing power consumption with a quality-of-service constraint. In particular, for a four-vehicle platoon communication, we derive closed-form solutions for optimal power allocation and present numerical results to verify the performance of the proposed FD relay vehicles. [ABSTRACT FROM AUTHOR]

Hypoxia is a common feature of the tumor microenvironment. Accumulating evidence has demonstrated hypoxia to be an important trigger of tumor cell invasion or metastasizes via hypoxia-signaling cascades, including hypoxia-inducible factors (HIFs). Microfluidic model can be a reliable in vitro tool for systematically interrogating individual factors and their accompanying downstream effects, which may otherwise be difficult to study in complex tumor tissues. Here, we used an in vitro model of microvascular networks in a microfluidic chip to measure the extravasation potential of breast cell lines subjected to different oxygen conditions. Through the use of HIF-1α knock-down cell lines, we also validated the importance of HIF-1α in the transmigration ability of human breast cell lines. Three human breast cell lines derived from human breast tissues (MCF10A, MCF-7 and MDA-MB-231) were used in this study to evaluate the role of hypoxia in promoting metastasis at different stages of cancer progression. Under hypoxic conditions, HIF-1α protein level was increased, and coincided with changes in cell morphology, viability and an elevated metastatic potential. These changes were accompanied by an increase in the rate of extravasation compared to normoxia (21% O2). siRNA knockdown of HIF-1α in hypoxic tumors significantly decreased the extravasation rates of all the cell lines tested and may have an effect on the function of metastatic and apoptotic-related cellular processes. [ABSTRACT FROM AUTHOR]

The importance of transforming growth factor beta-activated kinase 1 (TAK1) to cell survival has been demonstrated in many studies. TAK1 regulates signalling cascades, the NF-κB pathway and the mitogen-activated protein kinase (MAPK) pathway. TAK1 inhibitors can induce the apoptosis of cancerous cells, and irreversible inhibitors such as (5Z)-7-oxozeaenol are highly potent. However, they can react non-specifically with cysteine residues in proteins, which may have serious adverse effects. Reversible covalent inhibitors have been suggested as alternatives. We synthesised imidazopyridine derivatives as novel TAK1 inhibitors, which have 2-cyanoacrylamide moiety that can form reversible covalent bonding. A derivative with 2-cyano-3-(6-methylpyridin-2-yl)acrylamide (13h) exhibited potent TAK1 inhibitory activity with an IC50 of 27 nM. It showed a reversible reaction with β-mercaptoethanol, which supports its potential as a reversible covalent inhibitor. [ABSTRACT FROM AUTHOR]

This paper proposes hybrid beamforming designs for millimeter-wave (mmWave) multiple-input multiple-output (MIMO) backhaul systems equipped with uniform planar arrays (UPAs) of dual-polarization antennas at both the transmit and receive base stations. The proposed beamforming designs are to near-optimally solve optimization problems taking the dual-polarization UPA structure into account. Based on the solutions of optimization problems, this paper shows it is possible to generate the optimal dual-polarization beamformer from the optimal single-polarization beamformer sharing the same optimality. As specific examples, squared error and magnitude of inner product are considered respectively for optimization criteria. To optimize proposed beamformers, partial channel information is needed, and the use of low overhead pilot sequences is also proposed to figure out the required information. Simulation results verify that the resulting beamformers have the most uniform gain (with the squared error criterion) or the highest average gain (with the magnitude of inner product criterion) in the covering region with the UPA of dual-polarization antennas. [ABSTRACT FROM AUTHOR]

Morphogenesis involves a complex series of cell signaling, migration and differentiation events that are coordinated as tissues self-assemble during embryonic development. Collective cell movements such as those that occur during morphogenesis have typically been studied in 2D with single layers of cultured cells adhering to rigid substrates such as glass or plastic. In vivo, the intricacies of the 3D microenvironment and complex 3D responses are pivotal in the formation of functional tissues. To study such processes as collective cell movements within 3D multilayered tissues, we developed a microfluidic technique capable of producing complex 3D laminar multicellular structures. We call this technique “3D tissue-etching” because it is analogous to techniques used in the microelectromechanics (MEMS) field where complex 3D structures are built by successively removing material from a monolithic solid through subtractive manufacturing. We use a custom-designed microfluidic control system to deliver a range of tissue etching reagents (detergents, chelators, proteases, etc.) to specific regions of multilayered tissues. These tissues were previously isolated by microsurgical excision from embryos of the African claw-toed frog, Xenopus laevis. The ability to shape the 3D form of multicellular tissues and to control 3D stimulation will have a high impact on tissue engineering and regeneration applications in bioengineering and medicine as well as provide significant improvements in the synthesis of highly complex 3D integrated multicellular biosystems. [ABSTRACT FROM AUTHOR]

Abstract: Phagocytosis and subsequent degradation of pathogens by macrophages play a pivotal role in host innate immune response to microbial infections. To find small molecule regulators for the investigation of complicated phagocytic process, we screened our in-house chemical library and found chemicals which inhibit phagocytosis of zymosan by macrophages. A representative compound 5a reduced phagocytosis of zymosan in both peritoneal macrophages and RAW264.7 cells in a dose-dependent manner. Treatment of 5a led to downregulate the key regulators of phagocytosis, Rac1, Rac2 and Cdc42, and slightly reduced phosphorylation of Akt by zymosan. [Copyright &y& Elsevier]

Abstract: 1,3,4-Oxadiazole derivatives were found to enhance astrocyte differentiation in rat fetal neural stem cells (NSCs). Differentiation activity was assessed by immunocytochemistry and analysis of mRNA expression of astrocyte markers, GFAP and S100. Compounds 7 and 8 showed approximately a two-fold increase in astrocyte differentiation without engagement of neuronal differentiation and detectable cytotoxicity. [Copyright &y& Elsevier]

The TAM (Axl, Mer, and Tyro3) family is implicated in the survival and chemoresistance of tumours and has emerged as a potential therapeutic target. A novel series of 7-aryl-2-anilino-pyrrolopyrimidines were identified as potent Axl/Mer tyrosine kinase inhibitors without significant inhibition of Tyro3. A representative compound 27 exhibited IC50 values of 2 nM and 16 nM for Mer and Axl, respectively, and considerable inhibition for Mer phosphorylation in cells. Docking studies suggested that the formation of a salt bridge between the nitrogen of the aniline moiety with ASP678 of the Mer kinase domain as well as an interaction with the hinge region that most kinase inhibitors have in common would be essential to retain activity. These results could provide useful information for finding promising inhibitors of Axl/Mer for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the visual prognostic factors in patients with pseudophakic epiretinal membrane (ERM) after vitrectomy using spectral domain optical coherence tomography (SD-OCT). Method: A retrospective review of patients with pseudophakic ERM having undergone vitrectomy was conducted. Best corrected visual acuity (BCVA) and SD-OCT were conducted before and 1, 3, and 6 months after vitrectomy. Known visual prognostic factors, such as inner-retina irregularity index, central foveal thickness (CFT), central inner retinal layer thickness (CIRLT), cone outer segment tip defect length, and photoreceptor outer segment length, were reviewed and their correlation with BCVA was analyzed. Results: Forty-three patients (mean age: 64.88 ± 10.46 years) with pseudophakic ERM were included. BCVA significantly improved after vitrectomy (logMAR 0.30 ± 0.24 vs. 0.11 ± 0.14, p < 0.001). The preoperative high inner-retina irregularity index significantly correlated with poor postoperative BCVA in patients with pseudophakic ERM (correlation coefficient 0.583, p < 0.001). Postoperative improvements of inner retinal SD-OCT findings, such as inner-retina irregularity index, CFT, and CIRLT, were significantly associated with the amount of BCVA improvement after ERM surgery (correlation coefficients were as follows: inner-retina irregularity index – 0.711, p < 0.001; CFT – 0.462, p = 0.002; CIRLT – 0.596, p < 0.001). However, preoperative outer retinal SD-OCT findings were not associated with postoperative visual prognosis. Conclusion: From this study, we determined the visual prognostic factors of ERM surgery without confounding factors, such as visual acuity improvement following combined cataract surgery, and inner retinal SD-OCT findings more significantly associated with the visual prognosis of ERM surgery compared to outer retinal SD-OCT findings. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Evaluation against cell lines eliciting low response to erlotinib and miltefosine. • Amide analogs were active than ester analogs. • Most of the amide analogs were superior to erlotinib and miltefosine. • EGFR and Akt phorphorylation inhibition were not correlated to cells growth inhibition. Abstract Two series of erlotinib-alkylphospholipid hybrids were prepared and evaluated for their antiproliferative activities against a panel of four cell lines representing lung, breast, liver and skin cancers using erlotinib and miltefosine as reference standards. Amide analogs elicited more enhanced cytotoxic activity than analogous esters. Amide derivatives 8d and 8e exhibited promising broad-spectrum antiproliferative activity and higher efficacy than reference erlotinib and miltefosine. Their cellular GI 50 values was in the ranges of 24.7–46.9 μM and 26.8–43.1 μM for 8e and 8d respectively. Assay results of the inhibitory activity of the prepared compounds on EGFR kinase reaction and Akt phosphorylation in conjugation with statistical correlation analysis indicated that other mechanisms might contribute to their elicited cytotoxicities. In addition, statistical correlation analysis revealed that mechanisms of elicited cytotoxicities for amide series might be different from ester series. In addition, correlation analysis indicated variations in the mechanisms according to the types of cell line. [ABSTRACT FROM AUTHOR]

Abstract: As a model compound for the transcription factor hijacking mechanism of action of DNA damaging agent that simultaneously bind to the nuclear receptor, we designed and synthesized a chimeric molecule, RA-mustard, which can bind with both retinoic acid receptor α (RARα) and DNA. The interaction between RA-mustard with RARα was confirmed by binding assay using RARα-overexpressing cell extract. RA-mustard-modified DNA diminished the RARα-dependent luciferase expression in the RARα-abundant cells. [Copyright &y& Elsevier]