Meglumine-based Sustainable Three-component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1-b]quinazoline-3-carboxylates as a Sensing Probe for Cu2+ Ions.

An unprecedented meglumine-based three-component deep eutectic solvent (3c-DES) (MegPAc) was synthesized using meglumine, p-toluenesulfonic acid (PTSA), and acetic acid as a renewable, and non-toxic solvent. The exploitation of the MegPAc as an eco-friendly reaction media to construct a selective and sensitive small organic molecular sensing probe, namely, pyrazolo[5,1-b]quinazoline-3-carboxylates (PQCs) was executed. Captivatingly, the MegPAc served the dual role of solvent and catalyst, and it delivered the title components with 69-94 % yields within 67-150 minutes. Furthermore, a UV-visible study unfolds the selective detection of Cu2+ ions with our synthetic probe 4 ba and resulted in hypsochromic shift due to electrostatic interactions. Additionally, 1H NMR titration study and density functional theory (DFT) calculations were performed to attest the binding mechanism of sensing probe 4 ba and Cu2+ ions. Worthy of mention, this protocol unveils the efficacy of meglumine-based 3c-DES for the first time as a bio-renewable system to synthesize the PQCs.

Microwave-induced one-pot synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole hybrids as antiproliferative agents and density functional theory study.

Herein, we outline a highly efficient PEG-4000-mediated one-pot three-component reaction for the synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole derivatives (5a-r) at up to 96% yield as antiproliferative agents. This three-component protocol offers the advantages of an environmentally benign reaction, excellent yield, quick response time, and operational simplicity triggered by the copper catalyst under microwave irradiation. All the synthesized compounds were tested for antiproliferative activity against six human solid tumor cell lines, that is, A549 and SW1573 (nonsmall cell lung), HBL100 and T-47D (breast), HeLa (cervix), and WiDr (colon). Among them, six compounds, 5g-j, 5m, and 5p, demonstrated effective antiproliferative action with GI50 values under 10 µM. Furthermore, density functional theory (DFT) calculations were performed for all the synthesized molecules through geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The theoretical DFT calculation was performed using the DFT/B3LYP/6-31+G (d,p) basis set. Moreover, the biological reactivity of all the representative synthesized molecules was compared with the theoretically calculated quantum chemical descriptors and MESP 3D plots. We also investigated the drug-likeness characteristic and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. In general, our approach enables environmentally friendly access to 3-imidazolyl indole clubbed 1,2,3-triazole derivatives as prospective antiproliferative agents.

In silico and in vitro evaluation of newly synthesized pyrazolo-pyridine fused tetrazolo-pyrimidines derivatives as potential anticancer and antimicrobial agents.

Diversely functionalized pyrazolo-pyridine fused tetrazolo-pyrimidines 10aa-am and 10ba-bn were successfully synthesized via a catalyst-free synthetic protocol with moderate to very good yields. The compounds were evaluated for cytotoxicity against MCF-7 and HEK-293 cells using MTT assay. Among the tested compounds, 10ab (IC50- 23.83 µM) and 10ah (IC50- 23.30 µM) demonstrated the highest potency against MCF-7 cells, while 10bc (IC50- 14.46 µM) and 10bh (IC50- 2.53 µM) exhibited excellent cytotoxicity against HEK-293 cells. Additionally, antibacterial screening was performed against three Gram-negative bacteria (E. coli, P. aeruginosa, and S. enterica) and three Gram-positive bacteria (S. aureus, B. megaterium, and B. subtilis) using broth dilution method, while antifungal activity was assessed against three fungal strains (A. niger, Penicillium, and S. cerevisiae) using agar well diffusion method. In antimicrobial screening, the majority of the compounds demonstrated significant antibacterial efficacy compared to antifungal activity. We also conducted comprehensive computational studies, including DFT calculations, molecular docking and dynamics, and drug-likeness assessments. In the DFT study, compounds 10ac and 10bc displayed stable conformations, indicating their potential for higher therapeutic activity. Molecular docking analyses revealed compelling interactions, with compound 10ah demonstrating docking score -7.42 kcal/mol against catalytical domain PARP1 (PDB ID: 7KK4) and 10bh exhibiting a best docking score -10.77 kcal/mol against human corticotropin-releasing factor receptor 1 (PDB ID: 4Z9G). A 100 ns molecular dynamics (MD) simulation study of compounds 10ah and 10bh revealed the stable conformation and binding energy in a stimulating environment. In drug-likeness assessments, both the compounds 10ah and 10bh adhere all the established guidelines.Communicated by Ramaswamy H. Sarma.

Diversity-oriented synthesis of 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids as antimicrobial agents.

A straightforward and high yielding synthetic approach is employed to synthesize the novel 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids 7(a-t) as new antimicrobial agents with two pharmacophore in the effective two step synthesis. The first step is the four component one-pot synthesis of highly functionalized pyrazolo[5,1-b]quinazolines 5(a-j) catalysed by TBAB, with the advantages of an environmentally benign reaction, high yielding, quick reaction time, and operational simplicity. In the subsequent stage, CuSO4/NaAsc system was employed to synthesize the 1H-1,2,3-triazole tethered pyrazolo[1,5-b]quinazoline hybrids as 1H-1,2,3-triazoles are the structures of great diversity and importance in diverse therapeutics containing numerous biological activities. The antimicrobial activity of all the synthesized hybrid compounds have been preliminary tested using the broth dilution technique against two gram-positive and two gram-negative bacterial strains as well as two fungal strains. In comparison to standard drugs, the majority of compounds exhibited good to moderate activity. Among the all the compounds, 7a (MIC 18.54 µM) against Pseudomonas aeruginosa, 7j (MIC 89.76 µM) against Bacillus subtilis as well as Rhizopus oryzae and 7t (MIC 84.88 µM) against Aspergillus parasiticus have remarkable antimicrobial potency as compared to standard drug.

Ultrasound-promoted convenient and ionic liquid [BMIM]BF4 assisted green synthesis of diversely functionalized pyrazolo quinoline core via one-pot multicomponent reaction, DFT study and pharmacological evaluation.

An ultrasound-assisted green protocol for one-pot synthesis of a new series of pharmaceutically relevant pyrazolo quinoline derivatives (4a-t) were synthesized, characterized, and evaluated using DFT and biological activities. Pyrazolo quinoline derivatives (4a-t) were synthesized via a three-component tandem reaction of 1,3-dicarbonyl compound (1a-b), substituted aromatic aldehyde (2a-o), and 5-amino indazole (3a) in the presence of 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF4 ionic liquid in ethanol at ambient conditions. The main purpose of the present work is selective functionalization of pyrazolo quinoline (4a-t) core excluding another potential parallel reaction under environmentally benign reaction conditions. The present protocol shows features such as amphiphilic behavior of ionic liquid during reaction transformation, and reusability of the [BMIM]BF4 ionic liquid under mild reaction condition. All newly derived compounds were evaluated for their in vitro anti-inflammatory and antioxidant activity. Among them, compound 4c showed encouraging antioxidant activity compared with standard antioxidant ascorbic acid, and compounds 4n and 4r displayed very good anti-inflammatory activity compared with a standard drug. In this study, a theoretical computational density functional study was also executed to perform the geometry optimizations, frontier molecular orbital approach, and molecular electrostatic potential (MESP). The DFT study was carried out with the basis set DFT/B3LYP/6-31+G (d, p) level of theory. The quantum chemical descriptors (QCDS) and MESP diagrams were plotted to examine the biological reactivities of representative pyrazolo quinolines (4a-t).

Meglumine-Promoted Eco-Compatible Pseudo-Three-Component Reaction for the Synthesis of 1,1-Dihomoarylmethane Scaffolds and Their Green Credentials.

A simple, straightforward, and energy-efficient greener route for the synthesis of a series of biologically interesting functionalized 1,1-dihomoarylmethane scaffolds has been developed in the presence of meglumine as an efficient and eco-friendly organo-catalyst via one-pot pseudo-three-component reaction at room temperature. Following this protocol, it is possible to synthesize 1,1-dihomoarylmethane scaffolds of an assortment of C-H activated acids such as dimedone, 1,3-cyclohexadione, 4-hydroxy-6-methyl-2-pyrone, 4-hydroxycoumarin, and 1-phenyl-3-methyl-pyrazolone. The salient features of the present green protocol are mild reaction conditions, good to excellent yields, operational simplicity, easy isolation of products, no cumbersome post treatment, high atom economy, and low E-factor. In addition, this chemistry portrays several green advantages including the reusability of reaction media and product scalability, which makes protocol sustainably efficient. Additionally, several control experiments such as protection of catalyst reactive site, D2O exchange, and 1H NMR studies revealed possible pathways for meglumine-promoted reactions. Inspired by the natural physiological environment of 1,1-dihomoarylmethane scaffolds, we reconnoitered the biological profile of our compounds and synthesized compounds that were promising for their antiproliferative and antibacterial activities.

Unilateral multicystic renal dysplasia: Prenatal diagnosis on ultrasound.

Multicystic renal dysplasia (MCRD) is the most common cause of abnormally enlarged kidney, diagnosed on antenatal ultrasound examination. It is an abnormality of the embryonic development in which the renal parenchyma is substituted by nonfunctioning renal tissue made up of cysts which do not communicate with each other. Vesicoureteric reflux (VUR), pelviureteric junction obstruction, vesicoureteric junction obstruction, and ureterocele are the most commonly seen abnormalities in contralateral kidney. Here, we report a case of prenatal diagnosis of unilateral MCRD with VUR in contralateral kidney. In conclusion, we want to emphasize optimal use of ultrasound imaging to detect such abnormalities as early as possible to guide the proper management.

Role of CT scan in diagnosis of renal lymphangiectasia: our single-center experience.

BACKGROUND: Renal lymphangiectasia is rarely reported benign renal disorder of lymphatic malformation. Though found incidentally; it presents with nonspecific symptoms and shows characteristic findings in radiological imaging studies. AIM: Here, we report eight patients with symptoms, laboratory and imaging findings compatible with renal lymphangiectasia. This report describes clinical and laboratory characteristics, treatment, Imaging findings and outcome of a series of patients with renal lymphangiectasia and reviews the literature. METHODS AND MATERIAL: Eight patients (mean age 45 years, male:female ratio 3:1) from 1st January 2011 to 30th June 2016; showing renal lymphangiectasia as incidental finding on CT IVP were included in the series. Imaging and laboratory findings were reviewed. Two out of eight patients (25%) underwent aspiration of collection and laboratory findings confirmed the diagnosis of renal lymphangiectasia. Four out of eight patients (50%) did not undergo aspiration of fluid and were offered conservative treatment. Two out of eight patients (25%) were donors for renal transplantation who were managed conservatively. RESULTS: Renal lymphangiectasia was diagnosed on CT IVP. In each case, where aspiration of collection fluid was offered, the laboratory diagnosis of renal lymphangiectasia was confirmed and patients were managed conservatively. However, large collection in one patient was relieved by percutaneous aspiration. CONCLUSIONS: Renal lymphangiectasia can be diagnosed with CT scan and confirmed by laboratory tests. As it may be confused with other cystic lesions of kidney; proper diagnosis and exclusion of other differentials can be effectively offered by CT scan IVP, which can avoid unnecessary invasive treatment options.

Radial artery pseudoaneurysm: A rare complication after a single arterial puncture for blood-gas analysis.

With a reported incidence of 0.048%, radial artery pseudoaneurysm (PA) is a rare but serious complication of arterial cannulation. We report a case of PA developing after a single puncture of the right radial artery for arterial blood-gas analysis diagnosed by Doppler ultrasound in young male patient. The development of PA after puncture of radial artery for continuous blood pressure monitoring and serial blood-gas analysis has been reported in the past; however, to the best of our knowledge, there is only one case report of development of PA after a single arterial puncture for blood-gas analysis is reported in the past.

Renal Papillary Necrosis: Role of Radiology.

Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co-morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment.

Role of revascularization to improve left ventricular function.

Coronary revascularization to improve left ventricular (LV) function and improve mortality in patients with ischemic cardiomyopathy remains controversial, especially in the absence of angina or ischemia. A large body of observational evidence suggests that patients with dysfunctional but viable myocardium may experience improvement in mortality and LV function after revascularization. However, results of randomized trials conducted in the last decade dispute the value of viability testing or coronary revascularization in improving outcomes of patients with ischemic cardiomyopathy. However, because of the numerous methodological limitations of these studies, clinical equipoise persists regarding the role of coronary revascularization in certain patients.

Arrhythmogenic right ventricular dysplasia.

OPINION STATEMENT: Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic disorder that is characterized by ventricular arrhythmias and structural abnormalities of the right ventricle. Due to significant heterogeneity in its manifestation, the diagnosis of ARVD is challenging and requires a multifaceted approach to patient evaluation. It is important to not rush and diagnose ARVD prematurely, as the implications both for the patient and also for family members are enormous. Similarly, it is important for clinicians to be aware of this condition because it is potentially life threatening. There are three keys aspects to treatment once a diagnosis is established. The first issue concerns risk stratification and deciding whether to implant an implantable cardioverter defibrillator (ICD). We currently advise ICD implantation for probands who meet the full criteria for the disease, especially if they have experienced cardiac syncope, sustained ventricular tachycardia, or have severe right ventricular or left ventricular dysfunction. In addition, we feel there are sufficient observational clinical data and scientific data from animal models to advise that both competitive sports and high-level athletics be prohibited. We advise our patients to generally limit their activity to activities such as walking and golf. Finally, it is our opinion that most patients with ARVD should be treated with both a ß-blocker as well as an angiotensin-converting enzyme inhibitor, provided these drugs are well tolerated.

Management and results of sciatic nerve injuries: a 24-year experience.

OBJECT: The purpose of this retrospective clinical study was to present results and provide management guidelines for various types of sciatic injuries. METHODS: Over a 24-year period, 380 patients with sciatic nerve injuries were managed. In 230 patients (60%), the injury was at the buttock level, with injection injuries comprising more than half of these cases. Thigh-level sciatic injury was evaluated in 150 cases (40%) and was usually secondary to one of four main causes: 1) gunshot wound; 2) femur fracture; 3) laceration; or 4) contusion. Patients with partial deficits uncomplicated by severe pain or with significant spontaneous recovery or late referral were managed medically. Surgical exploration was not indicated in 23% of injuries at the thigh level and almost 50% of those at the buttock level. Most of these patients achieved partial but good spontaneous recovery, especially in the tibial division distribution. Surgical intervention was required for more complete and persistent deficits in either the tibial or peroneal distribution. Divisions of the sciatic nerve were split apart and evaluated independently. Management was guided by nerve action potential (NAP) recordings, which indicated whether neurolysis or resection of the lesion was required. Repair was then made by using sutures or more frequently by graft placement. In most cases in which neurolysis was performed because a positive NAP was recorded distal to the lesion, useful function was found in the peroneal distribution. Unfortunately, significant recovery occurred in only 36% of patients who received suture or graft repairs of the peroneal division. Good-to-excellent outcome was common for the tibial division, even in cases in which repair was proximal and required lengthy grafts. The relatively favorable recovery of tibial as opposed to peroneal divisions of the sciatic nerve occurred regardless of the level or mechanism of injury. CONCLUSIONS: Surgical exploration and, when necessary, repair of sciatic nerve injuries is worthwhile in selected cases.

Double-labeling of saphenous nerve neuron pools: a model for determining the accuracy of axon regeneration at the single neuron level.

We have developed a labeling procedure which accurately and consistently labels the original sensory pools projecting to their respective nerve branches as a model to quantify the accuracy of nerve regeneration at the single neuron level. Adult and juvenile rats had the saphenous branch of the femoral nerve transected just distal to the bifurcation of the nerve into a sensory branch (saphenous nerve) and a motor branch (nerve to the quadriceps muscle) and exposed to a 3% solution of 1,1'-di-octadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) for 1 h, and then reanastomosed. Two weeks later the sensory branch was redivided proximal to the previous site and labeled with a second tracer (5% fluorogold) using similar procedures. Five days later the animals were killed and cryostat sections were prepared and analyzed with a fluorescence microscope to score single- and double-labeled primary sensory neurons. The results show that the primary sensory neurons which project into the saphenous nerve can be reliably prelabeled by exposure of the saphenous nerve to DiI, and two weeks later approximately 99% of the same population of neurons can be labeled by exposure of the nerve to a second dye, fluorogold. This model system will be very powerful for future studies concerning target reinnervation following nerve regeneration.

Clinical and pathological analysis of spinal cord astrocytomas in children.

Twelve children with pathologically confirmed, well-differentiated spinal cord astrocytomas were studied, and correlations among the degree of resection, pathological characteristics, and time of recurrence were examined. Eight tumors were sampled for biopsy or subtotally resected, and 4 were thought to have been totally removed. Clinical recurrence was seen in 4 of 12 patients, 2 of whom died of their disease. The time to recurrence was 1, 2, 2, and 35 years, respectively. The other 8 children remain free of symptoms, with follow-up ranging from 6 months to 35 years (mean, 8.8 years). In 3 of 8 patients who underwent biopsy or subtotal resection, the tumor recurred, and 2 patients died, whereas there was one recurrence in the patients in whom a "total" resection had been obtained. The histologically well-differentiated nature of the lesions correlated well with the relatively prolonged clinical course seen in this series during the period of observation. The relatively long clinical courses seen in our limited series should be considered before high-risk therapy for spinal cord astrocytomas in children is implemented. The presence of four pilocytic astrocytomas in this group was of special interest, and it seems likely that these discrete neoplasms can be distinguished from the more infiltrating fibrillary astrocytic neoplasms by magnetic resonance imaging with enhancement with gadopentetate dimeglumine.

Spectroscopic studies of stellacyanin derivatives.

Two covalently modified derivatives of the apoprotein of the blue copper protein stellacyanin have been prepared. In one case, a dansyl group was linked to the cysteine at the copper binding site of apostellacyanin; in the other, a nitrophenol moiety has been attached to this same cysteine. Fluorescence yields and emission maxima of the dansylated protein and pK determinations of the nitrophenol group linked to the protein suggest that the solvent microenvironment at the copper binding site of apostellacyanin is quite similar to bulk water.