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Heterocyclic nucleus is vital in medicinal chemistry and has allured significant attention in chemotherapeutic domain. Oxadiazole, a five-membered nitrogen–oxygen-containing heterocyclic core has r...

[Abstract] Microtubule affinity-regulating kinase 4 (MARK4), a member of the serine/threonine kinase family, is an emerging therapeutic target in anticancer drug discovery paradigm due to its involvement in regulation of microtubule dynamics, cell cycle regulation, and cancer progression. Therefore, to identify the novel chemical architecture for the design and development of novel MARK4 inhibitors with concomitant radical scavenging property, a series of small-molecule arylaldoxime/5-nitroimidazole conjugates were designed and synthesized via multistep chemical reactions following the pharmacophoric hybridization approach. Compound 4h was identified as a promising MARK4 inhibitor with high selectivity toward MARK4 inhibition as compared to the panel of screened 30 kinases pertaining to the serine/threonine family, which was validated by molecular docking and fluorescence binding studies. The comprehensive cell-based examination divulged the promising apoptotic, antiproliferative, and antioxidant potential for the chemotype 4h. The compound 4h was endowed with the Ka value of 3.6 × 103 M–1 for human serum albumin, which reflects its remarkable transportation and delivery properties to the target site via blood. The present study impedes that in the future, such compounds may stand as optimized pharmacological lead candidates in drug discovery for targeting cancer via MARK4 inhibition with a remarkable anticancer profile. Council of Scientific and Industrial Research (India); 09/466 (0220) 2K19 EMR-I Government of India; EMR/2015/002372 Government of India; BT/PR12828/AAQ/1/622/2015 Indian Council of Medical Research; 45/9/2019-PHA/BMS

This article embodies the design and simulation of defected ground microstrip patch antenna with reconfigurable Hexa-band characteristics. Three PIN diodes are used in between two strips to perform the switching action and make the antenna resonates at six frequencies i.e. 1.09 GHz,1.6 GHz,1.8 GHz,3.05 GHz, 3.2 GHz and 4.6 GHz with the bandwidth of 250 MHz, 1360 MHz, 840 MHz, 810 MHz, 870MHz and 800MHz respectively. The maximum peak gain of 9.23 dBi has been obtained at 3.2 GHz resonating frequency. Designing and simulation of the proposed structure have been carried out by means of HFSS software (v.13). Due to a wide range of frequency reconfigurable (1–5 GHz) characteristics, this structure is extremely suitable for multiband wireless portable devices

Containers is the new buzz word within the computer technology space. With the technology growing at an exponential pace and within a short span of time, the industry has evolved from native to virtualized, to cloud and now to container technology. This evolution is focused more on decoupling the software with the hardware and making software or applications more lean and agile. Containers has done a lot of good in achieving this objective and has also helped to cope up with the deficiencies faced in virtualized and cloud based environment. This paper tries to do a literature review of the evolution of containers and will also attempt to analyze container eco system. This article will also discuss the differences between the containers and virtual machines and will highlight the efficiencies that container technology brings over the virtualized environment.

In continuation of our previous work, a series of furan-thiazolidinone hybrids was prepared by Knoevenagel condensation of 3-(furan-2-ylmethyl)-2-(phenylimino)-1, 3-thiazolidin-4-one with different aryl aldehydes in presence of strong base. Some members of the series exhibited remarkable antiamoebic activity and cell viability. Three compounds (3, 6 and 11) showed excellent binding energy for Entamoeba histolytica O-acetyle-l-serine sulfohydrolase and Entamoeba histolytica thioredoxin reductase. These compounds demonstrated significant inhibition of O-acetyle-l-serine sulfohydrolase. The promising antiamoebic activity and enzymatic assay of 3, 6 and 11 make them promising molecules for further lead optimization in the development of novel antiamoebic agents.

Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics.

Fuel wood scarcity in the Himalayan region is an established fact and mulberry (Morus alba L.) tree has a great potential in fuel and energy production. This study determines the role of indole-3-butyric acid (IBA) for rapid clonal propagation of mulberry for higher biomass and large-scale production; and examines the associated biochemical changes during rooting. The non-treated (control) and treated (1000, 2000 and 3000 IBA mg L−1) soft stem cuttings were cultured in mist chamber. After 50 days the rooting percentage, root number and root length were found to be higher in IBA-treated cuttings than in the non-treated ones. The rooting zone of IBA-treated and untreated cuttings were sampled at day 0 (prior to the culture in mist chamber), 15, 30, and 45 for estimation of total soluble indole content, peroxidase (POX), indole acetic acid oxidase (IAA-oxidase) and total soluble sugar (TSS). The total soluble indole, POX and IAA-oxidase were enhanced due to IBA. POX increased from day zero to day 45 of culture. IAA-oxidase kept increasing for 30 days and thereafter declined markedly. IBA initially increased TSS, which later decreased with passage of time till the 30th day both in IBA-treated and control cuttings. Thereafter, TSS content exhibited statistically non-significant variation at day 30 and 45 of culture. On the whole, IBA increased rooting phenomenon and activated carbohydrate metabolism. IAA-oxidase appears to trigger and initiate root primordia, whereas POX is involved in both initiation and elongation of roots.

The main aim of this research is to design a diplexer for 5G communications as proposed by TRAI 3.4 GHz to 3.6 GHz. The device consists of Wilkinson power divider, Band Pass Filters (BPF) with 20 MHz bandwidth. Filters and power combiners are realized with center frequency of the band (3.5 GHz). Uplink frequency choosen is 3.41 to 3.49 GHz and downlink frequency choosen is 3.51–3.59 GHz. In this device the two band pass filtering structures (for both uplink and downlink) are joined by a three port junction. The diplexer design is done by dividing the structure in two parts, to make the design more efficient and feasible. Eventually the whole diplexer is optimized to fit the desired specifications. In this paper band pass filters are designed using coupled lines, short circuited stubs and also with capacitive coupled resonators. Performance of the diplexer is compared among all three filter configurations.

This study presents a comparative account of biochemical responses evoked by a high-zinc-accumulating (HZnG) and a low-zinc-accumulating (LZnG) genotype of chickpea (Cicer arietinum L.) under conditions of zinc deficiency (0 mg ZnSO4 kg(-1) soil) and on exogenous zinc supply (2.5, 5, and 10 mg ZnSO4 kg(-1) soil), at different growth stages (pre-flowering, flowering, and post-flowering) of the crop. Both the genotypes exhibited significant variation in contents of chlorophyll, protein, nitrate, and leghemoglobin, and in the activity of enzymes (nitrate reductase, superoxide dismutase, and carbonic anhydrase), under zinc-limiting condition. The HZnG maintained a significantly higher level of biochemical parameters at deficient zinc levels, while LZnG was more affected by Zn deficiency (with reduced biochemical attributes), compared to HZnG. However, application of soil zinc alleviated the Zn-induced disturbance and improved the biochemical parameters in both genotypes. The differential biochemical response of plants to Zn deficiency indicated existence of genotypic variation in efficient utilization of the available Zn. The HZnG was more effective in overcoming Zn deficiency than the LZnG. This study suggests that metal-dependent biochemical parameters can be used as reliable indices for selection of genotypes with a better Zn utilization capacity, i.e., the Zn-efficient genotypes.

The liver is an integral organ in the body and plays a vital role for the metabolism of endogenous and exogenous agents. Drug-induced liver toxicity is one of most common cause of liver injury. It accounts for approximately one-half of the cases of acute liver failure and mimics all forms of acute and chronic liver disease. Hepatotoxicity is associated with the first line antituberculosis drugs such as isoniazid and rifampicin. Therefore, there is need of pharmacological interventions for the treatment of hepatotoxicity. The present study was designed to evaluate the hepatoprotective effect of the Centella asiatica extract on anti-TB drugs-induced hepatotoxicity. Hepatotoxicity was induced by administration of anti-TB drugs (isoniazid and rifampicin). Hepatotoxicity was assessed by significant elevation in oxidative stress, mitochondrial complex alterations and elevated levels of liver marker enzymes. Treatment with Centella asiatica (20, 40 mg/kg p.o.) attenuated the anti-TB drugs induced oxidative stress, mitochondrial complex alterations and elevated levels of liver marker enzymes (viz. SGOT, SGPT, ALP). Histopathological studies also show the promising effect. Therefore, the present study shows the hepatotoprotective effect of Centella asiatica. Therefore, Centella asiatica could be a new pharmacological intervention in the treatment of hepatotoxicity.

An in-house database of 520 compounds was docked against Entamoeba histolytica thioredoxin reductase (EhTrR), a promising target for the treatment of amoebiasis. Amongst these, some metronidazole (MTZ)-triazole hybrids were ranked high, with docking scores from -10.23 to -7.56. Studies of the binding orientations and conformations show that the head groups of MTZ-triazole hybrids interact with the arginine residues within the binding pocket of EhTrR, making it clear that such is the optimal and most reliable orientation for this class of compounds. The top-ten MTZ-triazole hybrids were then selected for evaluation of their activity against the HM1:IMSS strain of amoeba. The most active compound, 2-pyridyl-(1,2,3-triazolyl)metronidazole 10, with an IC50 value of 8.4 nM, was significantly more active than the standard drug MTZ alone. Docking studies revealed that compound 10 may act as an EhTrR inhibitor with activity in the nanomolar range and satisfactory ADME properties; it is a suitable candidate to be carried forward as a potential lead in the discovery of drugs to combat amoebiasis.

N-Acylhydrazones derived from 7-chloro-4-piperazin-1-yl-quinoline were synthesized and biologically evaluated for blood-stage of Plasmodium falciparum and Entamoeba histolytica trophozoites. N-Acylhydrazone F12 was found to inhibit the P. falciparum growth as well as its life cycle with good selectivity, which was achieved by inhibiting hematin formation. Compound F24 showed better IC50 value than the amoebicidal drug metronidazole.

The present study describes the synthesis and anti-amoebic activity of 4,6-disubstituted aminopyrimidines (1b–10b) and their sulphonamide derivatives (1–20). All the desired compounds were characterized by spectral data and their purity was confirmed by elemental analysis. The aim of the study was to explore the effect of the target compounds on in vitro growth of HM1:IMSS strain of Entamoeba histolytica. In vitro anti-amoebic activity was performed by microdilution method and the results were compared with standard drug metronidazole. The results revealed that sulphonamide derivatives (1–20) showed better activity than 4,6-disubstituted aminopyrimidines (1b–10b). 5 pyrimidine and 12 sulphonamide derivatives were better inhibitors of the growth of E. histolytica than the reference drug metronidazole (IC50 = 1.80 μM). The promising in vitro anti-amoebic activity of the compounds make them promising molecules for further lead optimization in the development of novel anti-amoebic agents, therefore, it is hoped that these preliminary results could help in designing better molecules with an enhanced anti-amoebic activity.

In the quest for potent anti-amoebic agents, some 1,3,4-thiadiazole derivatives were synthesized and characterized by spectral data. The purity of the compounds was confirmed by elemental analysis. All the compounds were screened in vitro against HM1:IMSS strain of Entamoeba histolytica by microdilution method. The results revealed that compounds 1 (IC50 = 0.670 μM), 3 (IC50 = 1.60 μM) and 8 (IC50 = 0.522 μM) had much better anti-amoebic activity than the reference drug metronidazole (IC50 = 1.80 μM). Further, cytotoxicity of the compounds having IC50 value less than metronidazole was assessed by MTT assay on human breast cancer MCF-7 cell line and all the compounds were found low cytotoxic in the concentration range of 2.5–250 μM. Preliminary results indicate that these three compounds (1, 3 and 8) may be subjected to further investigations and it may be hoped that the present study will stimulate efforts towards the development of novel effective anti-amoebic agents.

Mannich base derivatives of 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-(3H)-thione with substituted piperazine were synthesized and characterized. In vitro antiamoebic activity was performed against HM1: IMSS strain of Entamoeba histolytica and the cytotoxicity of the compounds having IC50 value less than metronidazole was assessed by MTT assay on human breast cancer MCF-7 cell line. The results revealed that compounds 2, 3 and 5 were found to be better inhibitors of E. histolytica than the reference drug metronidazole and found low cytotoxic in the concentration range of 2.5–250 μM. This study suggests the possibility of developing 1,3,4-oxadiazole analogues as potential drug candidates.

Pyrazolo[3,4-d]pyrimidine analogues were synthesized by treating 3-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4-amine with different sulfonyl chlorides and triethylamine in dry dichloromethane. The structure of all the compounds was elucidated by spectral data and their purity was confirmed by elemental analysis. In vitro antiamoebic activity was performed against HM1:IMSS strain of Entamoeba histolytica and two compounds, 4 (IC50 = 0.57) and 6 (IC50 = 0.68), were found better inhibitors than the reference drug metronidazole (IC50 = 1.80). Further, both the compounds (4 and 6) were low cytotoxic against the human breast cancer MCF-7 cell line in the concentration range of 2.5–250 μM. These preliminary results reveal that pyrazolo[3,4-d]pyrimidine analogues could help in designing better molecules with enhanced antiamoebic activity.

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A series of 1,2,4-triazole derivatives containing thiosemicarbazone linkage was synthesized and evaluated for their in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. All the compounds were capable of inhibiting the growth of E. histolytica out of which four compounds (IC(50)=0.28-1.38 μM) were found to have better efficacy than the standard drug Metronidazole (IC(50)=1.8 μM). Cytotoxicity of the active compounds was assessed by MTT assay using human breast cancer MCF-7 cell line, which revealed that all the compounds were low cytotoxic in the concentration range of 2.5-250 μM.

In an effort to develop effective antiamoebic agents, some hydrazones and azoles containing pyridyl moiety were synthesized and screened for in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. Among all the compounds, only five compounds (1, 3, 5, 9 and 11) were found to be better inhibitors of growth of E. histolytica than the reference drug metronidazole. The cytotoxic studies of these compounds on human breast cancer MCF-7 cell line revealed that all the compounds were low-cytotoxic in the concentration range of 2.5-250 μM.