Dihydrobenzothiazole coupled N-piperazinyl acetamides as antimicrobial agents: Design, synthesis, biological evaluation and molecular docking studies.

Substituted saturated N-heterocycles have gained momentum as effective scaffolds for the development of new drugs. In this study, we coupled partly saturated benzothiazoles with substituted piperazines and evaluated their antimicrobial activity. Following a three-step reaction sequence from commercially available cyclic 1,3-diones, a series of novel 2-[4-substituted-1-piperazinyl]-N-(7-oxo-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)acetamides (7a-af) were synthesised. 2-Amino-5,6-dihydro-benzo[d]thiazol-7(4H)-ones, obtained through the condensation of cyclohexane-1,3-diones with thiourea, were acetylated with chloroacetic chloride and then reacted with N-substituted piperazines 6a-p to give the desired products 7a-af in excellent yields. All 32 new compounds were fully characterised by their 1 H-nuclear magnetic resonance (NMR), 13 C-NMR and high-resolution mass spectrometry spectra. The synthetic compounds 7a-af were tested in vitro for their efficacy as antimicrobials against pathogenic strains of Gram-positive and Gram-negative bacteria, Streptococcus mutans and Salmonella typhi, respectively, as well as against fungal strains, including Candida albicans 3018 and C. albicans 4748. Ciprofloxacin and fluconazole served as the reference drugs. While compounds 7c and 7l showed inhibition against fungal strains with zones of inhibition of 11 and 1 mm, respectively, four analogues (7d, 7l, 7n, and 7r) demonstrated strong antibacterial action (zone of inhibition in the range of 10-15 mm). Three compounds (7j, 7l, and 7w) also exhibited moderate antitubercular activity (MIC: 6.25 µg/mL) against Mycobacterium tuberculosis H37Rv. Molecular docking investigations and the predicted physicochemical and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties for the potent compounds made this scaffold useful as a pharmacologically active framework for the development of potential antimicrobial hits.

Carbon Dots' Potential in Wound Healing: Inducing M2 Macrophage Polarization and Demonstrating Antibacterial Properties for Accelerated Recovery.

Bacterial infections and persistent inflammation can impede the intrinsic healing process of wounds. To combat this issue, researchers have delved into the potential use of carbon dots (CDs) in the regulation of inflammation and counteract infections. These CDs were synthesized using a microwave-assisted hydrothermal process and have demonstrated outstanding antibacterial and antibiofilm properties against Gram-positive and Gram-negative bacteria. Additionally, CDs displayed biocompatibility at therapeutic concentrations and the ability to specifically target mitochondria. CD treatment effectively nullified lipopolysaccharide-triggered reactive oxygen species production by macrophages, while simultaneously promoting macrophage polarization toward an anti-inflammatory phenotype (M2), leading to a reduction in inflammation and an acceleration in wound healing. In vitro scratch assays also revealed that CDs facilitated the tissue-repairing process by stimulating epithelial cell migration during reepithelialization. In vivo studies using CDs topically applied to lipopolysaccharide (LPS)-stimulated wounds in C57/BL6 mice demonstrated significant improvements in wound healing due to enhanced fibroblast proliferation, angiogenesis, and collagen deposition. Crucially, histological investigations showed no indications of systemic toxicity in vital organs. Collectively, the application of CDs has shown immense potential in speeding up the wound-healing process by regulating inflammation, preventing bacterial infections, and promoting tissue repair. These results suggest that further clinical translation of CDs should be considered.

Efficient Green Synthesis, Anticancer Activity, and Molecular Docking Studies of Indolemethanes Using a Bioglycerol-Based Carbon Sulfonic Acid Catalyst.

Indolemethane derivatives are significant molecules in the study of N-heterocyclic chemistry. Herein, we designed and developed a highly efficient green synthesis of indolemethane compounds using a recyclable biodegradable glycerol-based carbon solid acid catalyst under solvent-free conditions at room temperature for 5 min with excellent yields. The synthesized compounds were subjected to cytotoxic activity against prostate (DU145), hepatocellular carcinoma (HepG2), and melanoma (B16) cell lines. The highest cytotoxicity effects were found with 1k (1.09 µM) and 1c (2.02 µM) against DU145, followed by 1a, 1d, 1f, 1n, and 1m between 5.10 and 8.18 µM concentrations. The anticancer activity is validated using molecular docking simulations, and comparing binding energies with the standard drug doxorubicin suggests that the title compounds are well fitted into the active site pocket of the target molecules..

Toxicological evaluation of therapeutically active zinc oxide nanoflowers in pre-clinical mouse model.

Our earlier reports established that zinc oxide nanoflowers (ZONF) show significant pro-angiogenic properties, where reactive oxygen species, nitric oxide and MAPK-AKT-eNOS cell signaling axis play an essential task. Considering the significance of angiogenesis in healthcare, our research group has recently demonstrated the in vivo therapeutic application of ZONF (10 mg/kg b.w.) for treating peripheral artery disease. Moreover, based on the angio-neural crosstalk between vascular and neuronal systems, we have further demonstrated the neuritogenic and neuroprotective characteristics of pro-angiogenic nanoflowers (10 mg/kg b.w.) for the treatment of cerebral ischemia. However, it is crucial for a therapeutic material to be non-toxic for its practical clinical applications and therefore assessment of its in vivo toxicity and adverse effect is highly important. Herein, for the first time, we investigate a detailed nanotoxicology of therapeutically active ZONF in Swiss albino mice to evaluate their safety profile and comprehend their aspects for future clinical applications. The maximum tolerated dose (MTD) of ZONF was found to be 512.5 mg/kg b.w. which was employed for acute exposure (2 weeks), showing slight toxicity. However, sub-chronic (4 weeks) and long term chronic (8-12 weeks) studies of nanoflowers exhibited their non-toxic nature particularly at lower therapeutic doses (1-10 mg/kg b.w.). Additionally, in depth genotoxicity study revealed that lower therapeutic dose of ZONF (10 mg/kg b.w.) did not exhibit significant toxicity even in genetic level. Overall, the present nanotoxicology of ZONF suggests their high biocompatible nature at therapeutic dose, offering the basis of their future clinical applications in ischemic and other vascular diseases.

Chemometric assisted natural DES based VA-DLLME-LC-MS/MS method for the quantitative determination of Garcinol in biofluids/tissues: A practical application to pharmacokinetics and biodistribution studies.

Garcinol (GAR) is a polyisoprenylated benzophenone obtained from Garcinia indica used as anti-oxidant and anti-inflammatory in traditional medicine and due to these activities, it possesses anticancer properties. It is considered to be a next generation epigenetic drug. A green solvent based analytical method which is efficient, sophisticated, and highly enriched has been developed for the quantitative analysis of GAR in biological samples (plasma, liver, kidney and spleen) with the use of deep eutectic solvent (DES) for its extraction. A series of 23 DESs were synthesized and out of which, Thymol (Th)-Terpeniol (T), 2:1 molar ratio with a more hydrophobic environment and high interaction efficiency between GAR and DES was identified for the better extraction from mice plasma and tissue samples. The Design of Experiment approaches like placket-burmann design and central composite design were used to optimize the method conditions. The method validation characteristics, such as limit of detection (0.193-0.237 ng/mL), limit of quantification (0.644-0.697 ng/mL), lower limit of quantification (0.5 ng/mL), broad range of linearity with R2 (0.9994-0.9997) with a percent recovery not less than 87% was observed, which are well within the acceptance criteria for a bioanalytical method. The enrichment factor is upto 53-60 folds, with high extraction efficiency (89-97%). The measurement uncertainty was estimated with an expanded uncertainty ranged between 10.9%-19.0%. The method developed and validated was effectively applied to examine the pharmacokinetic and biodistribution patterns for GAR in mice.

In vitro and in vivo antimalarial activity of green synthesized silver nanoparticles using Sargassum tenerrimum - a marine seaweed.

Green nanotechnology has recently attracted a lot of attention as a potential technique for drug development. In the present study, silver nanoparticles were synthesised by using Sargassum tenerrimum, a marine seaweed crude extract (Ag-ST), and evaluated for antimalarial activity in both in vitro and in vivo models. The results showed that Ag-ST nanoparticles exhibited good antiplasmodial activity with IC50 values 7.71±0.39 µg/ml and 23.93±2.27 µg/ml against P. falciparum and P. berghei respectively. These nanoparticles also showed less haemolysis activity suggesting their possible use in therapeutics. Further, P. berghei infected C57BL/6 mice were used for the four-day suppressive, curative and prophylactic assays where it was noticed that the Ag-ST nanoparticles significantly reduced the parasitaemia and there were no toxic effects observed in the biochemical and haematological parameters. Further to understand its possible toxic effects, both in vitro and in vivo genotoxicological studies were performed which revealed that these nanoparticles are non-genotoxic in nature. The possible antimalarial activity of Ag-ST may be due to the presence of bioactive phytochemicals and silver ions. Moreover, the phytochemicals prevent the nonspecific release of ions responsible for low genotoxicity. Together, the bio-efficacy and toxicology outcomes demonstrated that the green synthesized silver nanoparticles (Ag-ST) could be a cutting-edge alternative for therapeutic applications.

Clastogenic, aneugenic, and tubulin polymerization properties of di-(2-ethylhexyl) phthalate and dibutyl phthalate.

Phthalate compounds were found to disrupt the endocrine system and alter transcriptomes during human embryonic development. In our previous work, we have isolated and reported two such phthalates di-(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) from Brevibacterium mcbrellneri bacteria and evaluated their bioactive properties. Naturally derived phthalates might be less toxic compared with synthesized molecules. We have investigated biologically isolated phthalates to understand the possible genotoxic effects in mice and further investigated in silico binding and polymerization of ß-tubulin. Three sub-lethal concentrations of DEHP (150 µM, 175 µM, and 200 µM) and DBP (10 µM, 15 µM, and 30 µM) were studied. The results showed that the phthalates were found to be highly genotoxic in nature. However, the pattern of genotoxic effects was not found to be dose-dependent in the induction of chromosome aberrations (CA), micronuclei (MN), and changes in the mitotic index (MI) in cells. In silico studies of phthalates on polymerization of ß-tubulin suggested that both DBP and DEHP were able to interact with the hydrogen bonds and make strong van der Waals interactions with ß-tubulin thereby possibly causing destabilization of microtubule network. Our study suggests that these phthalates might be playing an important role in normal cell division thereby showing highly genotoxic effects.

Aryl-n-hexanamide linked enaminones of usnic acid as promising antimicrobial agents.

Lichen secondary metabolites are well explored medicinal agents with diverse pharmacological properties. One of the important antibiotic lichen secondary metabolites is usnic acid. Its diverse medicinal profiles prompted us to explore it as a potential antitubercular molecule. Towards this direction, continuing our efforts on the discovery and development of new analogs with potent antitubercular properties we designed, synthesized, and evaluated a set of 37 usnic acid enaminone-coupled aryl-n-hexanamides (3-39). The study yielded a 3,4-dimethoxyphenyl compound (13, 5.3 µM) as the most active anti-TB molecule. The docking studies were performed on 7 different enzymes to better understand the binding modes, where it was observed that compound 13 bound strongly with glucose dehydrogenase (Gscore: - 9.03). Further antibacterial investigations revealed compound 2 with potent inhibition on Salmonella typhi and Bacillus subtilis (MIC 3 µM) and MIC values of 7 and 14 µM on Streptococcus mutans and Escherichia coli respectively. Compound 19 (3-F-5-CF3-phenyl) displayed encouraging antibacterial profiles against E. coli, S. typhi and S. mutans with MIC values of 10 µM respectively. Interestingly, compound 20 (2,6-difluorophenyl) also displayed good antibacterial activity against E. coli with an MIC value of 6 µM. These encouraging pharmacological results will help for better designing and developing usnic acid-based semi-synthetic derivatives as potential antimicrobial agents. A set of 37 new usnic acid enaminone-coupled aryl-n-hexanamides were synthesized and evaluated as potential antimicrobial agents. Compound 13 was identified as the most active antitubercular molecule. 13 was further docked against 7 different enzymes of tuberculosis. The molecule displayed maximum binding energy with the enzyme Glucose dehydrogenase (Gscore: - 9.03), indicating that these hexanamides possibly act by inhibiting the glucose metabolic pathway of the bacterium. Surprisingly, the intermediate hexanoic acid 2 was identified as potent antibacterial agent, acting on both gram-positive and gram-negative bacterial strains (3-14 µM). The active compounds may be subjected to structural iterations to develop further leads.

Tin-loaded mesoporous silica nanoparticles: Antineoplastic properties and genotoxicity assessment.

Nanotechnology has immensely advanced the field of cancer diagnostics and treatment by introducing potential delivery vehicles as carriers for drugs or therapeutic agents. In due course, mesoporous silica nanoparticles (MSNs) have emerged as excellent vehicles for delivering drugs, biomolecules, and biomaterials, attributed to their solid framework and porosity providing a higher surface area for decorating with various functional ligands. Recently, the metal tin (Sn) has gained huge importance in cancer research owing to its excellent cytotoxicity and ability to kill cancer cells. In the present work, we synthesized MSNs, conjugated them with organotin compounds, and characterized them using various physicochemical techniques. Subsequently, the biological evaluation of MSN (S1), MSN-MP (S2) and tin-conjugated MSNs (S3: MSN-MP-SnPh3) (MP = 3-mercaptopropyltriethoxysilane) revealed that these nanoconjugates induced cytotoxicity, necrosis, and apoptosis in MCF-7 cells. Moreover, these nanoconjugates exhibited anti-angiogenic properties as demonstrated in the chick embryo model. The increase of reactive oxygen species (ROS) was found as a one of the plausible mechanisms underlying cancer cell cytotoxicity induced by these nanoconjugates, encouraging their application for the treatment of cancer. The tin-conjugated MSNs demonstrated less toxicity to normal cells compared to cancer cells. Furthermore, the genotoxicity studies revealed the clastogenic and aneugenic effects of these nanoconjugates in CHO cells mostly at high concentrations. These interesting observations are behind the idea of developing tin-conjugated MSNs as prospective candidates for anticancer therapy.

Synthesis and evaluation of novel almazole D analogs as anticancer agents.

Novel almazole D-amide conjugates, esters, and N-alkylated analogs were synthesized and investigated for their anticancer activity against seven cancer cell lines. Among the series, compounds 5g and 5m showed significant anticancer activities against multiple cell lines with moderate selectivity indices. Compound 5g had IC50 values of 5.86 ± 0.31, 9.94 ± 0.06, 12.74 ± 0.12, and 9.40 ± 0.03 µM against the B16-F10, DU145, HeLa, and LC-540 cell lines, respectively, while compound 5m showed IC50 values of 6.35 ± 0.09, 9.17 ± 0.11, 9.00 ± 0.011, 19.65 ± 0.63, 8.13 ± 0.04, and 11.56 ± 0.01 µM against B16-F10, DU145, HeLa, HepG2, LC-540, and SK-BR-3 cells, respectively. Compared to almazole D, which only showed significant activity against B16-F10 cells (IC50 = 9.05 ± 0.008 µM), the synthesized analogs showed improved anticancer activity against multiple cell lines. The kinase inhibition assay coupled with the docking studies revealed that epidermal growth factor receptor (EGFR) kinase inhibition via interaction with amino acid residue T790 on the EGFR is one of the possible mechanisms by which 5g exerts its anticancer potential. The ADMET prediction and drug-likeness of the analogs project the synthesized analogs as promising agents, which can be further developed for application in cancer therapy.

I2/TBHP mediated domino synthesis of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-aryl/alkyl benzamides and evaluation of their anticancer and docking studies.

A novel I2/TBHP mediated domino synthesis of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-phenyl benzamides by reaction of isatins with o-amino N-aryl/alkyl benzamides was described. This was the first application of o-amino N-aryl/alkyl benzamides participating in oxidative rearrangement with isatins for synthesis of desired products. The synthesized compounds contained amide and quinazoline units and their combination resulted in molecular hybridization of two important pharmacophores. In this study, the synthesized compounds 3a-r were screened for cytotoxicity against four cancer cell lines A549, DU145, B16-F10, and HepG2 and also non-cancerous cell line CHO-K1. The compounds 3c, 3l and 3o gave promising results. The in silico molecular docking studies (PDB ID 1N37) also validated the anticancer activity of these compounds showing good binding affinity with target DNA and by acting as DNA intercalators.

Facet-Dependent Bactericidal Activity of Ag3PO4 Nanostructures against Gram-Positive/Negative Bacteria.

Ag3PO4 nanostructures (APNs) containing silver (Ag metal; of the noble metal families) have the potential to exhibit enzyme-mimetic activity. A nanostructure shape, including its surface facets, can improve the bioactivity of enzyme mimicry, yet the molecular mechanisms remain unclear. Herein, we report facet-dependent peroxidase and oxidase-like activity of APNs with both antibacterial and biofilm degrading properties through the generation of reactive oxygen species. Cubic APNs had superior antibacterial effects than rhombic dodecahedral shapes when inhibiting Gram-positive and Gram-negative bacterial pathogen proliferation and biofilm degradation. A similar performance was observed for rhombic dodecahedral shapes, being greater than tetrahedral-shaped APNs. The extent of enzyme-mimetic activity is attributed to the facets {100} present in cubic APNs that led the peroxide radicals to inhibit the proliferation of bacteria and degrade biofilm. These facets were compared to rhombic dodecahedral APNs {110} and tetrahedral APNs {111}, respectively, to reveal a facet-dependent enhanced antibacterial activity, providing a plausible mechanism for shape-dependent APNs material enzyme-mimetic effects on bacteria. Thus, our research findings can provide a direction to optimize bactericidal materials using APNs in clinically relevant applications.

In Vitro and In Vivo Anticancer and Genotoxicity Profiles of Green Synthesized and Chemically Synthesized Silver Nanoparticles.

Silver nanoparticles were green synthesized (Ag-PTs) employing the crude extract of Padina tetrastromatica, a marine alga, and their anticancer and safety profile were compared with those of chemically synthesized silver nanoparticles (Ag-NPs) by in vitro and in vivo models. Ag-PT exhibited potent cytotoxicity against B16-F10 (IC50 = 3.29), MCF-7 (IC50 = 4.36), HEPG2 (IC50 =3.89), and HeLa (IC50 = 4.97) cancer cell lines, whereas they exhibited lower toxicity on normal CHO-K1 cells (IC50 = 5.16). The potent anticancer activity of Ag-PTs on cancer cells is due to the liberation of ions from the nanoparticles. Increased ion internalization to the cells promotes reactive oxygen species (ROS) production and ultimately leads to cell death. The in vitro anticancer results and in vivo melanoma tumor regression study showed significant inhibition of melanoma tumor growth due to Ag-PT treatment. Ag-PT is involved in the upregulation of the p53 protein and downregulation of Sox-2 along with the Ki-67 protein. The antitumor effects of Ag-PTs may be due to the additional release of ions at a lower pH of the tumor microenvironment than that of the normal tissue. The results of safety investigations of Ag-PT by studying mitotic chromosome aberrations (CAs), micronucleus (MN) induction, and mitotic index (MI) demonstrated Ag-PT to be less genotoxic compared to Ag-NP. The bioefficacy and toxicology outcomes together demonstrated that the green synthesized silver nanoparticles (Ag-PTs) could be explored to develop a biocompatible, therapeutic agent and a vehicle of drug delivery for various biomedical applications.

3-Aryl-substituted imidazo[1,2-a]pyridines as antituberculosis agents.

Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3-aryl-substituted imidazo[1,2-a]pyridines as potent antituberculosis agents. A small library of 3-aryl-substituted imidazo[1,2-a]pyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd-catalyzed C-N coupling reactions. The compounds thus obtained were evaluated against Mycobacterium tuberculosis H37Rv. Compound 26 was identified as an antituberculosis lead with a minimum inhibitory concentration of 2.3 µg/ml against M. tuberculosis H37Rv. This compound showed a selectivity index of 35. The docking of 26 in the active site of the M. tuberculosis cytochrome bc1 complex cytochrome b subunit (Mtb QcrB) revealed key π-π interactions of compound 26 with the Tyr389 and Trp312 residues of Mtb QcrB.

Anti-hyperglycemic and genotoxic studies of 1-O-methyl chrysophanol, a new anthraquinone isolated from Amycolatopsis thermoflava strain SFMA-103.

The compound 1-O-methyl chrysophanol (OMC) which belongs to a class of hydroxyanthraquinones was isolated from Amycolatopsis thermoflava strain SFMA-103 and studied for their anti-diabetic properties. OMC was evaluated as an anti-diabetic agent based on in silico studies which initially predicted the binding energy with α-amylase (-188.81 KJ mol-1) and with α-glucosidase (70.53 KJ mol-1). Further, these results were validated based on enzyme inhibition assays where OMC demonstrated enzyme inhibitory activity towards α-amylase (IC50 3.4 mg mL-1) and α-glucosidase (IC50 38.49 µg mL-1). To confirm the anti-diabetic activity, in vivo studies (oral dose in Wistar rats) revealed that OMC inhibited significantly the increase in glucose concentration at 100 mg/kg as compared to starch control (p < 0.05). Further, to understand the safety of OMC as a therapeutic agent, the genotoxic analysis was performed in both in vitro Chinese Hamster Ovary cells (250, 500, and 1000 µM/mL) and in vivo Swiss albino mice (250, 500, and 1000 mg/kg). In vitro results showed that OMC concentration of up to 250 µM/mL did not elicit significant changes in CAs, MI, and MN counts in CHO cells. Similarly, in mice experiments (i.p. injection), no significant changes in CAs, MI, and MN induction were observed till 500 mg/kg of OMC when compared with chrysophanic acid (Cy) (200 mg/kg). In addition, mice that received the lowest dose of OMC (250 mg/kg) did not show any histological changes in liver, kidney, and heart. The study concluded that five times higher therapeutic dose (100 mg/kg) of OMC can be utilized against hyperglycemia with no genotoxic effects.

Quantitative Variable Assessment of Patellar Instability: An MRI-Based Study.

OBJECTIVE. The purpose of this study was to investigate the reproducibility of three quantitative MRI parameters associated with patellar instability and to determine whether they measure anatomic predisposition to patellar instability individually or in combination with the other parameters. MATERIALS AND METHODS. In this retrospective study, 100 patients diagnosed with a patellar dislocation injury and 100 age- and sex-matched control patients were examined using MRI. The distance between the tibial tubercle and posterior cruciate ligament (TT-PCL), distance between the tibial tubercle and trochlear groove (TT-TG), and TG depth (trochlear dysplasia) were measured independently by three fellowship-trained musculoskeletal radiologists. Intraclass correlation coefficient (ICC) was used to assess intraobserver and interobserver reliability. The parameters in both groups were tested for interdependence on each other and were compared for prevalence and association with patellar instability. RESULTS. All three parameters showed almost perfect intraobserver (TT-PCL ICC, ≥ 0.88; TT-TG ICC, 0.96; trochlear dysplasia ICC, ≥ 0.92) and interobserver (TT-PCL ICC, 0.82; TT-TG ICC, 0.94; trochlear dysplasia ICC, 0.91) reliability and were significantly more common in the patellar instability group. Trochlear dysplasia had the highest association with patellar instability, both as a unique parameter and in pairwise combination with an abnormal TT-TG. Optimal cutoff thresholds for normal TT-TG and TT-PCL were 15.00 mm or less and 21.30 mm or less, respectively. The optimal normal cutoff threshold for evaluating trochlear dysplasia via trochlear depth was 4.95 mm or more. CONCLUSION. Patellar instability is multifactorial. Highly reproducible parameters derived from MRI reveal both unique and overlapping anatomic predispositions, and considering all parameters together may help individualize patient management when selecting orthopedic procedures.

Synthesis of novel 4,5-dihydropyrrolo[1,2-a]quinoxalines, pyrrolo[1,2-a]quinoxalin]-2-ones and their antituberculosis and anticancer activity.

A facile strategy was developed for the synthesis of biologically important 4,5-dihydropyrrolo[1,2-a]quinoxalines and pyrrolo[1,2-a]quinoxalin]-2-ones by treating 2-(1H-pyrrol-1-yl)anilines with imidazo[1,2-a]pyridine-3-carbaldehyde or isatin, using amidosulfonic acid (NH3 SO3 ) as a solid catalyst in water at room temperature. The protocol has been extended to electrophile ninhydrin. The catalyst could be recycled for six times without the loss of activity. The compounds were evaluated for their antituberculosis, antibacterial, and anticancer activities. It is worth noting that compounds 3d and 3e demonstrated a minimum inhibitory concentration value of 6.25 µM against Mycobacterium tuberculosis H37Rv, whereas compounds 3d, 3g, 5d, 5e, and 5i showed a remarkable inhibition of A549, DU145, HeLa, HepG2, MCF-7, and B16-F10 cell lines, respectively. Staphylococcus aureus was inhibited by compounds 5b, 5e, 5d, 5g, and 5l at 32 µg/ml.

Out of pocket expenditure and its associated factors in neonates admitted to neonatal intensive care unit of tertiary care government hospital of Agra District, Uttar Pradesh.

BACKGROUND: Neonatal health remains a thrust area of public health, and an increased out-of-pocket expenditure (OOPE) may hamper efforts toward universal health coverage. Public spending on health remains low and insurance schemes few, thereby forcing impoverishment upon individuals already close to poverty line. OBJECTIVE: To determine catastrophic health expenditure (CHE) in neonates admitted to the government neonatal intensive care unit (NICU) and factors associated with of out-of-pocket expenditure. METHODS: This cross-sectional study was conducted in a governmental NICU at Agra from May 2017 to April 2018. A sample of 450 neonatal admissions was studied. Respondents were interviewed for required data. OOPE included costs at NICU, intervening health facilities, and transport as well. SPSS version (23.0 Trial) and Epi Info were used for analysis. RESULTS: Of the 450 neonates analyzed, the median total OOPE was Rs. 3000. CHE was found among 55.8% of cases with 22% spending more than their household monthly income. On binary logistic regression, a higher total OOPE of Rs. 3000 or more was found to be significantly associated with higher odds of residing outside Agra (adjusted odds ratio [AOR] = 1.829), delay in first cry (AOR = 1.623), referral points ≥3 (AOR = 3.449), private sector as first referral (AOR = 2.476), and when treatment was accorded during transport (AOR = 1.972). CONCLUSIONS: OOPE on neonates amounts to a substantial figure and is more than the country average. This needs to be addressed sufficiently and comprehensively through government schemes, private enterprises, and public-private partnerships.