Synthesis of Hydrazide Derivative of Betulinic Acid, Its Organometallic Complexes, Characterization and Bioassay.

Betulinic acid and its derivatives comprehend an immense prospective toward the development of cytotoxic, antiviral, antimicrobial and antioxidant agents. Cisplatin (cytotoxic drug) divert the attentions to develop organometallic compounds with pronounced biological activities. The current study was aimed for the first time to synthesize, characterize and evaluate biologically a series of metal (Fe, Cu, Zn, Sn and Sb) complexes of betulinic acid hydrazide. First step involved the formation of hydrazide derivative of betulinic acid (ligand) by modification at C-28 carboxylic acid moiety of betulinic acid with hydrazine followed by the synthesis of its metal complexes using salts of different metals (Fe, Cu, Zn, Sn and Sb). Physical state, melting point, Fourier-transform infrared (FT-IR) and 1 H nuclear magnetic resonance (1 H-NMR) spectral techniques were used to characterized the ligand and its metal complexes. Agar well diffusion method and agar tube dilution assay were performed to evaluate its antibacterial and antifungal activities respectively. DPPH assay was carried out to develop antioxidant properties by the reported methods.

Organotin (IV) complexes with sulphonyl hydrazide moiety. Design, synthesis, characterization, docking studies, cytotoxic and anti-leishmanial activity.

Due to a lack of therapeutic options for the pathological condition of leishmaniasis, which is characterized by polymorphic lesions and skin surface infections, Leishmania genus parasites damaged dermis and mucosa. There was a need to synthesize and characterize some new complexes. This study evaluated the biological activities preferably anti-Leishmanial activity of organotin (IV) containing sulphonyl hydrazide derivatives. A series of six new organotin (IV) complexes 1-6 labeled as R2SnL2; R = Methyl (1), Butyl (2), Phenyl (3) and R3SnL; R = Methyl (4), Butyl (5), Phenyl (6) has been synthesized as reflux method derived from N'- (2,4-dinitrophenyl)-4-methylphenylsulfonylhydrazide (L). All compounds were characterized through FT-IR, 1HNMR, 13CNMR, and elemental analysis. Structural analysis confirms the formation of six complexes (1-6). All derivatives have been screened for their pharmacological activities. Interestingly, compound 1 showed promising activity against leishmania promastigotes with low cytotoxicity. All results were further elaborated through docking studies performed on leishmania donovoni synthetase PDB: ID 3QW3 that acts as an essential building block for the viability of Leishmania promastigotes. This research effectively synthesized sulphonyl hydrazide ligand and its six new organotin (IV) derivatives, which were tested for biological properties such as antibacterial, anti-fungal, anti-oxidant, and ideally anti-leishmanial activity and cytotoxicity. Studies have confirmed that these compounds have the potency to be a good candidate against leishmaniasis. Computational studies were carried out to recognize the binding affinities for leishmania donovoni synthetase.Communicated by Ramaswamy H. Sarma.

Prospective Application of Two New Pyridine-Based Zinc (II) Amide Carboxylate in Management of Alzheimer's Disease: Synthesis, Characterization, Computational and in vitro Approaches.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative illness described predominantly by dementia. Even though Alzheimer's disease has been known for over a century, its origin remains a mystery, and researchers are exploring many therapy options, including the cholinesterase technique. A decreased acetylcholine ACh neurotransmitter level is believed to be among the important factors in the progression of Alzheimer's disease. METHODS: In continuation of synthesizing potential anti-Alzheimer agents and known appreciative pharmacological potential of amide-containing compounds, this study presents the synthesis of two novel amide-based transition metal zinc (II) complexes, AAZ7 and AAZ8, attached with a heterocyclic pyridine ring, which was synthesized and characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, 1H_NMR, and 13C_NMR. FT-IR spectroscopic records showed the development of bidentate ligand as Δν value was decreased in both complexes when compared with the free ligand. Both of the synthesized complexes were analyzed for acetylcholinesterase and butyrylcholinesterase inhibitory potential along with the antioxidizing activity. RESULTS: Importantly, the complex of AAZ8 exhibited more potent activity giving IC50 values of 14 µg/mL and 18µg/mL as AChE and BChE cholinesterase inhibitors, respectively, when compared with standard positive control galantamine. Interestingly, AAZ8 also displayed promising antioxidant potential by showing IC50 values of 35 µg/mL for DPPH and 29 µg/mL for ABTS in comparison with positive control ascorbic acid. CONCLUSION: Herein, we report two new amide carboxylate zinc (II) complexes which were potentially analyzed for various biological applications like acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory potentials, and antioxidant assays. Computational docking studies also simulated results to understand the interactions. Additionally, thermodynamic parameters utilizing molecular dynamic simulation were performed to determine the ligand protein stability and flexibility that supported the results. Studies have shown that these compounds have the potential to be good anti-Alzheimer candidates for future studies due to inhibition of cholinesterase enzymes and display of free radical scavenging potential against DPPH as well as ABTS free radicals.

Zinc metal carboxylates as potential anti-Alzheimer's candidate: in vitro anticholinesterase, antioxidant and molecular docking studies.

In search of suitable therapy for the management of Alzheimer's disease, this study was designed to evaluate metal complexes against its biochemical targets. Zinc metal carboxylates (AAZ1-AAZ6) were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. Therefore, these compounds were also screened for ABTS and DPPH free radical scavenging activity. In AChE inhibition assay, we noticed encouraging IC50 values of 33.07 and 59.52 µM for compounds AAZ5 and AAZ3, respectively. However, when we tested BChE activity, we observed an outstanding IC50 of 0.056 µM for compound AAZ6. Amazingly all of our compounds (AAZ1-AAZ6) were proved to be strong antioxidants which actively supplement the anti-Alzheimer's activity. The majority of our compounds exhibited lower IC50 values than the standard ascorbic acid in both DPPH and ABTS assays. We also correlated our results with molecular docking studies. Results elaborated that AAZ1 and AAZ5 exhibit strong interactions with amino acids HIS 362, HIS 398, GLU 306 ARG 289 and SER 237 inside binding pocket of targeted protein. In remarks, we can claim that our synthesized zinc metal carboxylates have strong potency to manage Alzheimer's disease on both anticholinesterase and antioxidant targets. Communicated by Ramaswamy H. Sarma.

Evaluation and management consideration for children who are visually impaired.

Clinical low vision evaluations provided by optometrists or ophthalmologists trained and experienced in low vision rehabilitation care should be recommended for all children with a visual impairment, regardless of the cause of their vision loss, their age or the severity of their additional disabilities. This article discusses an effective model for pediatric vision rehabilitation service.

Synthesis of 2-nitro aniline derivative of 3, 4, 5-trihydroxybenzoic acid, its metal complexes, characterization and bioassay.

Present research work discloses new and novel synthesis of metal complexes (Fe, Cu, Zn, Sb and Sn) of 3, 4, 5-trihydroxybenzoic acid derivative containing aniline moiety with substitution at C-7 position of 3, 4, 5-trihydroxybenzoic acid in order to enhance its biological activities by coupling therapeutic values of transition metals as well. In vitro antibacterial and antifungal activities of these compounds has been performed by using agar diffusion method against different bacterial and fungal strains. The free radical scavenging assay was performed by using 2, 2-diphenyl-1-picryl-hydrazyl (DPPH). Cytotoxic action of compounds was assessed by utilizing the standard MTT (3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyl-tetrazolium bromide) colorimetric assay. The structure of newly synthesized complexes were confirmed by using IR and 1HNMR spectral analysis.

Zinc and iron complexes of oleanolic acid, (OA) attenuate allergic airway inflammation in rats.

Oleanolic acid (OA) is a hydroxyl pentacyclic triterpene acid (HTAs) used in various ailments. Inflammatory diseases may be profoundly influenced by iron (Fe) and zinc (Zn) status. We studied the anti-asthmatic effects of two metal complexes (Fe and Zn) of OA in the ovalbumin (OVA)-induced rat model. Delayed type hypersensitivity (DTH) was measured. Total and differential leucocyte count was done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of pro-inflammatory cytokines were measured in lung tissue by reverse transcription polymerase chain reaction. The levels of cyclooxygenase-2 (COX-2), immunoglobulin E (IgE) and 5-lipoxygenase (5-LOX) were estimated by enzyme linked immunosorbent assay. Splenocyte proliferation was performed through BrdU uptake method and nitric oxide levels were measured by colorimetric assay kit. The acute toxicity study was also done for the complexes. The asthmatic group developed allergic airway inflammation shown by increased DTH and inflammatory markers in blood and BALF. OA + Fe and OA + Zn displayed significant decrease in DTH, NO, expression of IL-4, 5, 13, 17, toll-like receptor-2, nuclear factor-kappa B and tumor necrosis factor-α; serum IgE, COX-2, and 5-LOX. The metal complexes also attenuated OVA-stimulated splenocyte proliferation. While no hepatotoxic or nephrotoxic potential was shown by OA + Fe and OA + Zn. Our findings indicate that both OA + Fe and OA + Zn possess significant anti-asthmatic effect which may be ascribed to its immunomodulatory and anti-inflammatory features.

Corrigendum: Ursolic Acid Hydrazide Based Organometallic Complexes: Synthesis, Characterization, Antibacterial, Antioxidant, and Docking Studies.

[This corrects the article DOI: 10.3389/fchem.2018.00055.].

Low vision rehabilitation: An update.

This article provides information concerning issues related to the care of individuals who are visually impaired. Issues reviewed include determining who should be referred for vision rehabilitation services, Charles Bonnet syndrome, visual acuity, contrast sensitivity and visual field testing along with Useful Field of View testing. This article also discusses technology advances that can enhance the visual functioning of individuals who are visually impaired, including how these advances can help drivers with visual impairments to continue to safely operate motor vehicles, at least on a limited basis. Finally, resources that are available to both encourage and motivate patients to take advantages of vision rehabilitation services are reviewed.

Ursolic Acid Hydrazide Based Organometallic Complexes: Synthesis, Characterization, Antibacterial, Antioxidant, and Docking Studies.

In thecurrent research work,eleven metal complexes were synthesized from the hydrazide derivative of ursolic acid. Metal complexes of tin, antimony and iron were synthesized and characterized by FT-IR and NMR spectroscopy. The antibacterial and antioxidant activities were performed for these complexes, which revealed that the metal complexes synthesized are more potent than their parent compounds. We observed that antioxidant activity showed by triphenyltin complex was significant and least activity have been shown by antimony trichloride complex. The synthesized metal complexes were then evaluated against two Gram-negative and two Gram-positive bacterial strains. Triphenyl tin complex emerged as potent antibacterial agent with MIC value of 8 µg/ml each against Shigellaspp, Salmonella typhi and Staphylococcus aureus. While, the MIC value against Streptococcus pneumoniae is 4 µg/ml. Computational docking studies were carried out on molecular targets to interpret the results of antioxidant and antibacterial activities. Based on the results, it may be inferred that the metal complexes of ursolic acid are more active as compared to the parent drug and may be proved for some other pharmacological potential by further analysis.

Carica papaya ameliorates allergic asthma via down regulation of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS levels.

BACKGROUND: Natural products have a prime importance as an essential source for new drug discovery. Carica papaya leaves (CPL) have been used to treat inflammation in traditional system of medicine. AIM/HYPOTHESIS: Current study evaluates the anti-inflammatory and immunomodulatory effects of CPL extract using mouse model of ovalbumin- (OVA) induced allergic asthma. METHODS: All the mice were intraperitoneally sensitized and subsequently given intranasal challenge with OVA except the control group. Group-III and -IV were treated for seven consecutive days with CPL extract and methylprednisolone (MP), respectively. At the end of study, histopathological examination of the lungs was performed and inflammatory cell counts were done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS were measured using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Results showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and goblet cell hyperplasia after treatment with CPL extract. We also found significant suppression of total and differential leukocyte counts in both blood and BALF samples of CPL extract treated group. CPL extract also alleviated the expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS. Similarly, treatment with MP, used as a reference drug, also significantly ameliorated all the pro-inflammatory markers. CONCLUSION: Current study shows that CPL extract possesses anti-inflammatory effect in mouse model of allergic airway inflammation by down-regulating IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS expression levels.

Feasibility of retinal screening in a pediatric population with type 1 diabetes mellitus.

PURPOSE: To study the feasibility of using a nonmydriatic camera to screen children with type 1 diabetes mellitus (DM1) as young as 2 years for diabetic retinopathy. METHODS: Prospective pilot imaging study involving children with DM1 aged 2 to 17 years. The screening consisted of: (1) intake form; (2) measurement of blood pressure, pulse, and oximetry; (3) assessment of visual acuity (SIMAV, Padova, Italy); and (4) nonmydriatic color imaging (Canon CX-1 45° 15.1 megapixel camera; Canon Corp., Tokyo, Japan). Images were assessed for signs of diabetic retinopathy and graded for quality on a scale of 1 to 5 by two clinicians. Kappa coefficient was calculated to determine inter-observer agreement. RESULTS: One hundred four of 106 (98%) children underwent imaging (mean age: 11.1 years, 51% male, 88% white). One (1%) child had nonproliferative diabetic retinopathy and 2 (1.9%) had incidental findings. Only 62% of children had an eye examination within the past year, with children with DM1 for more than 5 years significantly more likely to have done so (P = .03). Children who had an eye examination within the past year were significantly older than their counterparts (P = .01). Images of high quality (grades 4 and 5) were acquired in 178 (86%) eyes, and images of some clinical value (grades ≥ 2) were obtained in 207 (99.5%) eyes. Inter-observer agreement for image quality was 0.896. CONCLUSIONS: The feasibility of using a nonmydriatic camera to screen children as young as 2 years for changes related to diabetic eye disease was demonstrated. Nonmydriatic imaging may supplement standard dilated clinical ophthalmology examinations for select patient populations.

Fundus autofluorescence and colour fundus imaging compared during telemedicine screening in patients with diabetes.

We investigated the use of fundus autofluorescence (FAF) imaging in screening the eyes of patients with diabetes. Images were obtained from 50 patients with type 2 diabetes undergoing telemedicine screening with colour fundus imaging. The colour and FAF images were obtained with a 15.1 megapixel non-mydriatic retinal camera. Colour and FAF images were compared for pathology seen in nonproliferative and proliferative diabetic retinopathy (NPDR and PDR, respectively). A qualitative assessment was made of the ease of detecting early retinopathy changes and the extent of existing retinopathy. The mean age of the patients was 47 years, most were male (82%) and most were African American (68%). Their mean visual acuity was 20/45 and their mean intraocular pressure was 14.3 mm Hg. Thirty-eight eyes (76%) did not show any diabetic retinopathy changes on colour or FAF imaging. Seven patients (14%) met the criteria for NPDR and five (10%) for severe NPDR or PDR. The most common findings were microaneurysms, hard exudates and intra-retinal haemorrhages (IRH) (n = 6 for each). IRH, microaneurysms and chorioretinal scars were more easily visible on FAF images. Hard exudates, pre-retinal haemorrhage and fibrosis, macular oedema and Hollenhorst plaque were easier to identify on colour photographs. The value of FAF imaging as a complementary technique to colour fundus imaging in detecting diabetic retinopathy during ocular screening warrants further investigation.

Software-assisted analysis during ocular health screening.

OBJECTIVE: To describe the use of software-assisted analysis of non-mydriatic 45° color fundus images during comprehensive ocular screening. MATERIALS AND METHODS: Software-driven filters (blue [490 nm; nerve fiber layer], green [550 nm; neural retina], and red [610 nm; pigmented retina/choroid]) and an "emboss" (topographic changes) digital filter were used to enhance image analysis during ocular health screening performed using a Canon (Tokyo, Japan) 8.2-megapixel non-mydriatic retinal camera. Intraocular pressure (model TX-f full auto non-contact tonometer; Canon) and visual acuity (SIMAV, Padova, Italy) were also determined. An on-site medical director analyzed the collected data, provided immediate subject feedback, and made recommendations and referrals for general or specialty ophthalmology clinics. RESULTS: Software-assisted analysis was performed on color images from 128 veterans (mean age, 37.5 years; 66% male; 43% white). Software filters allowed efficient image analysis at a rate of 26 eyes/h. Thirteen (10.2%) persons had a finding consistent with a vision-threatening disease and were referred for a dilated fundus examination. CONCLUSIONS: Software-assisted screening permits thorough and efficient evaluation of ocular health during an ocular screening event.

Ocular telehealth screenings in an urban community.

The current U.S. economic recession has resulted in a loss of income, housing, and healthcare coverage. Our major goal in this socioeconomic setting was to provide ophthalmic remote health screenings for urban soup kitchen and homeless populations in order to identify and refer undetected vision-threatening disease (VTD). We assessed visual acuity, blood pressure, pulse/oxygen saturation, body mass index, and intraocular pressure for 341 participants at soup kitchens as part of the homeless outreach program in Newark, NJ. History of diabetes, hypertension, and smoking, last ocular examination, and ocular history were noted. Imaging was performed with an 8.2 megapixel non-mydriatic retinal camera with high-speed Internet ready for off-site second opinion image evaluation. Positive VTD findings were identified in 105 participants (31%) (mean age, 53.6 years), of whom 78% were African American, 73% males, and 62% smokers. We detected glaucoma in 34 participants (32%), significant cataract in 22 (21%), diabetic retinopathy in 5 (5%), optic atrophy in 1 (1%), age-related macular degeneration in 1 (1%), and other retinal findings in 43 (41%). The incidence of VTDs was higher among this cohort than among study groups in previous screenings (31% vs. 12%). This finding shows an increase in ocular morbidity in a younger, at-risk population with elevated rates of hypertension, diabetes, and smoking. Functional visual impairment was 2.5 times higher than the national average (16% vs. 6.4%). Comprehensive, community-based screenings can provide more sensitive detection of VTDs in high-risk groups with low access to ophthalmic care and can be an integral part of recession solutions for improving healthcare.

Software-assisted optic nerve assessment for glaucoma tele-screening.

Increased optic nerve head (ONH) cup-to-disc ratio (CDR) may indicate glaucoma but evaluation needs to be performed by a trained examiner. This research assessed new software to calculate CDR from ONH images. Digital stereoscopic ONH images from 28 subjects acquired during screening using a nonmydriatic 45-degree camera with 8.2-Megapixel resolution (Canon, Tokyo, Japan) were analyzed by 3 individuals with different levels of ophthalmic training: glaucoma specialist (GS), an optometrist (OD), and trainees. Images were logged and accessed by raters masked to each other's evaluations. Images from two groups were included: normal-appearing ONH (Group 1) and confirmed glaucoma (Group 2). All images were captured in DICOM format. Images were evaluated on a 32-bit, 1,600 x 1,200-pixel resolution monitor. EyeScape software (v. 7.4, Synemed, Inc., Benicia, CA) was used for CDR analysis. Software CDR determination requires an operator to place ONH disc and cup contour lines. Once lines were placed, the software provided CDR calculations (range 0.00-1.00). A total of 84 ONH evaluations were analyzed. Overall CDR mean, standard deviation, standard error of the mean, and mean difference from GS CDR evaluations were determined. Reproducibility was similar for all operators. The trainee had a small, statistically significant greater CDR in group 1 and 2 evaluations. Evaluation of ONH images for CDR can be performed using EyeScape software, by individuals with different levels of ophthalmic training. Accurate determination of CDR is important in tele-screening for vision-threatening diseases, and can aid in identifying subjects with suspicious ONH in need of specialty eye care.