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.

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.

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.

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.

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.

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.

Synthesis and efficacy of pyrvinium-inspired analogs against tuberculosis and malaria pathogens.

Herein, we report the synthesis and evaluation of pyrvinium-based antimalarial and antitubercular compounds. Pyrvinium is an FDA approved drug for the treatment of pinworm infection, and it has been reported to have antiparasitic and antimicrobial activities. Pyrvinium contains quinoline core coupled with pyrrole. We replaced the pyrrole with various aryl or heteroaryl substituents to generate pyrvinium analogs. The profiling of these compounds against malaria parasite P. falciparum 3D7 revealed analogs with better antimalarial activity than pyrvinium pamoate. Compound 14 and 16 showed IC50 of 23 nM and 60 nM against P. falciparum 3D7, respectively. These compounds were also effective against drug-resistant malaria parasite P. falciparum Dd2 with IC50 of 53 nM and 97 nM, respectively. The cytotoxicity against CHO-K1, HEK and NRK-49F cells revealed better selectivity index for these new analogs compared to pyrvinium. Additionally, this series of compounds showed activity against M. tuberculosis H37Rv; particularly compounds 10, 13, 14 and 16 showed equipotent antitubercular activity to that of pyrvinium pamoate. The compounds 14 and 16 should be taken forward as leads for further optimization.

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.

Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents.

(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 µM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 µM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 µM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.

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.

Zoledronic acid induces cytogenetic toxicity in male germline cells of Swiss albino mice.

This study mainly focuses on the cytogenetic toxicity induction by zoledronic acid (ZA), a nitrogen containing bisphosphonate (N-BPs) in the male germline cells of Swiss albino mice. A single intraperitoneal exposure with three different doses of ZA (2, 4, and 8 mg/kg body weight), toxicity was assessed by analyzing spermatogonial metaphase chromosome aberrations at 24 h, aberrant primary spermatocytes at week 4, and abnormal spermatozoa at week 8 posttreatment. Cyclophosphamide (40 mg/kg) and 0.9% NaCl were used as positive and vehicle controls respectively in the study. The results showed that there was a significant induction in the number of chromosomal aberrations especially at two doses of ZA (4 and 8 mg/kg) after 24 h in the spermatogonial cells (p < 0.001) compared to vehicle control. The transmission genetic damages were noticed as aberrant spermatocytes with atypical bivalents (X-Y/autosomal asynapsis) at 4 mg/kg of ZA (p < 0.01) and at 8 mg/kg of ZA (p < 0.001) at week 4 posttreatment. A statistically significant higher number of abnormal spermatozoa (sperm) were also noticed at week 8 posttreatment of both at 4 and 8 mg/kg of ZA (p < 0.001). Hence, from these genotoxicity studies, it can be concluded that ZA is genotoxic in male germline cells and has the potential of transmitting the genotoxic effects from spermatogonial cells to sperm in male Swiss mice.

Potential of the Bioinspired CaCO3 Microspheres Loaded with Tetracycline in Inducing Differential Cytotoxic Effects toward Noncancerous and Cancer Cells: A Cytogenetic Toxicity Assessment Using CHO Cells in Vitro.

Calcium carbonate (CaCO3)-based materials as feasible pH-sensitive drug carriers, which can actively dissolve in an acidic microenvironment of cancer cells, are finding increasing importance. This has drawn our interest in the development of a bioinspired polypeptide- mediated method to design calcium carbonate microspheres loaded with tetracycline (CaCO3-TC) with an aim to explore its safe application in cancer therapeutics. Its therapeutic application in cancer patients essentially demands its safety information on the normal cells. Herein our study presents the in vitro genetic toxicological information on CaCO3-TC using noncancerous mammalian CHO cells in comparison to bare TC at three different concentrations (100, 200, and 300 µM) selected based on the cytotoxicity data (MTT). Assessment of various end points like chromosome aberrations, micronucleus, mitotic index and effects on cell cycle distribution after 24 h post-treatment demonstrates a significant reduction in clastogenic ( P < 0.001), aneugenic potential ( P < 0.05), and nonmitotoxic nature of CaCO3-TC than that of bare TC. Noticeably, as inferred from the FACS analysis on cancer cells, G2/M phase accumulation in breast cancer cells (MDA-MB-231), and at G1 phase in cervical cancer cells (HeLa) reveal its potential anticancer property. On the other hand, the genotoxicity studies illustrate protective effects of CaCO3-TC on noncancerous cells. While the pH-dependent dissolution property of the CaCO3 matrix encasing tetracycline results in higher toxicity on cancer cells, the near neutral pH in the case of normal cells prevents complete dissolution of CaCO3 thereby not allowing the encapsulated TC to adequately interact with the cells. Therefore, thus assembled CaCO3 spheres not only provide a way for facile encapsulation of tetracycline under mild conditions but also result in an effective matrix for differential toxicity toward normal and cancer cells justifying its clinical development as a novel target-specific drug in therapeutic applications for metastatic cancers.

Costunolide induces micronuclei formation, chromosomal aberrations, cytostasis, and mitochondrial-mediated apoptosis in Chinese hamster ovary cells.

Costunolide (CE) is a sesquiterpene lactone well-known for its antihepatotoxic, antiulcer, and anticancer activities. The present study focused on the evaluation of the cytogenetic toxicity and cellular death-inducing potential of CE in CHO cells, an epithelial cell line derived from normal ovary cells of Chinese hamster. The cytotoxic effect denoting MTT assay has shown an IC50 value of 7.56 µM CE, where 50% proliferation inhibition occurs. The oxidative stress caused by CE was confirmed based on GSH depletion induced cell death, conspicuously absent in N-acetylcysteine (GSH precursor) pretreated cells. The evaluation of genotoxic effects of CE using cytokinesis block micronucleus assay and chromosomal aberration test has shown prominent induction of binucleated micronucleated cells and aberrant metaphases bearing chromatid and chromosomal breaks, indicating CE's clastogenic and aneugenic potential. The apoptotic death in CE treated cells was confirmed by an increase in the number of cells in subG1 phase, exhibiting chromatin condensation and membranous phosphatidylserine translocation. The apoptosis induction follows mitochondrial mediation, evident from an increase in the BAX/Bcl-2 ratio, caspase-3/7 activity, and mitochondrial membrane permeability. CE also induces cytostasis in addition to apoptosis, substantiated by the reduced cytokinetic (replicative indices) and mitotic (mitotic indices and histone H3 Ser-10 phosphorylation) activities. Overall, the cellular GSH depletion and potential genotoxic effects by CE led the CHO cells to commit apoptosis and lowered cell division. The observed sensitivity of CHO cells doubts unintended adverse effects of CE on normal healthy cells, suggesting higher essentiality of further studies in order to establish its safety efficacy in therapeutic explorations.

Assessment of disease aggression in cystic pancreatic neuroendocrine tumors: A CT and pathology correlation study.

BACKGROUND/OBJECTIVES: There are inconsistencies in the literature regarding the clinical significance of cystic components in pancreatic neuroendocrine tumors (NET). This may be related to differences in the identification of cystic NET through imaging and/or pathology. Tumors may also be microscopically or macroscopically cystic. Our primary objective is to determine radiology-pathology correlation for the identification of cystic components. Our secondary objective is to determine if cystic components are associated with indices of tumor aggression. METHODS: 60 tumors with correlative surgical pathology were assessed retrospectively for cystic components on CT and pathology. Tumor was categorized as solid or cystic on CT and pathology. If cystic on pathology, cystic components were categorized as macroscopic or microscopic. Cystic components were estimated as <50% and ≥50% tumor volume. WHO/Hochwald grade and presence of metastases were used to stratify disease aggression. Associations were tested with Chi square/Fisher's exact test and differences were tested with t-test/Wilcoxon rank sums test. RESULTS: There is moderate agreement between CT and histology for presence of cystic components. Discrepancies were mostly attributable to the presence of microscopic cystic components in tumors appearing solid on CT. There was no difference in size between cystic and solid tumors on CT or pathology. No association between CT-determined cystic components and tumor grade was found. Tumors with cystic components (cystic by CT, and macroscopically cystic by pathology) demonstrated less association with metastases than solid tumors. CONCLUSIONS: Cystic components, comprising ≥50% of the tumor by CT and observed macroscopically on pathology, are associated with less aggressive disease.

Synthesis and biological evaluation of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thioglycosides.

In the present study, the synthesis of 1, 3, 4-thiadiazole-based thioglycosides were accomplished in good yields with employing a convergent synthetic route. The starting material 5-amino-1, 3, 4-thiadiazole-2-thiol and followed by a series of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thiols (4a-4j) were synthesized with different fatty acid chlorides. The glycosylation of compounds 4a-4j were achieved with trichloroacetimidate methodology. Antimicrobial and cytotoxicity activities of title compounds were evaluated. Among the entire compounds lauric acid and myristic acid derivatives showed good and moderate antimicrobial activity. In case of cytotoxicity results of compounds 8a-8j and 9a-9j, the acetate protected short chain (C6:0, C8:0, C10:0) compounds and the free hydroxyl long chain saturated (C16:0, C18:0) and unsaturated (C18:1, C22:1) compounds exhibited good activity against different cancer cell lines. Further, the free hydroxyl compounds 9a, 9c-9j did not show any toxicity towards normal CHO-K1 cell line whereas acylated compounds 8a-8j exhibited toxicity.

Molecular Engineering of Tetracyclic 2,3-Dihydro-1H-benzo[2,3]-benzofuro[4,5-e][1,3]oxazine Derivatives: Evaluation for Potential Anticancer Agents.

Water-mediated one-pot Mannich type condensation of dibenzo[b,d]furan-2-ol with different amines resulted in a large library of novel 2,3-dihydro-1H-benzo[2,3]benzofuro[4,5-e][1,3]oxazine derivatives in moderate to excellent yields. The ortho-aminomethylation of the dibenzofuranols proceeded smoothly in the presence of various aromatic/aliphatic amines and paraformaldehyde, followed by cyclization. All the newly synthesized tetracyclic 2,3-dihydro-1H-benzo[2,3]benzofuro[4,5-e][1,3]oxazine derivatives were chemically characterized and screened for their cytotoxicity activity by cell viability assay (MTT test) against three human cancer cell lines and antibacterial activity by determining the minimum inhibitory concentration (MIC) against four bacterial strains. Among all the derivatives, MCV-24 showed promising anticancer activity by inhibiting the cell proliferation of an ovarian cancer cell line (SKOV3) with an IC50 value at 7.5 µM, whereas MCV-24 to MCV-30 derivatives showed moderate activity against a lung cancer cell line (A549) with an IC50 value ranging from 11 to 15.9 µM. Besides MCV-29, -30, and -31 also exhibited broad-spectrum antibacterial activity. Among all new compounds, MCV-24-30 showed promising anticancer and MCV-29-31 antibacterial activity.

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids.

The synthesis of five novel methyl 10-undecenoate-based lipoconjugates of phenolic acids from undecenoic acid was carried out. Undecenoic acid was methylated to methyl 10-undecenoate which was subjected to a thiol-ene reaction with cysteamine hydrochloride. Further amidation of the amine was carried out with different phenolic acids such as caffeic, ferulic, sinapic, coumaric and cinnamic acid. All synthesized compounds were fully characterized and their structures were confirmed by spectral data. The anti-oxidant activity of the synthesized lipoconjugates of phenolic acids was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and also by the inhibition of linoleic acid oxidation in micellar medium by differential scanning calorimetry (DSC). The prepared compounds were also screened for their cytotoxic activity against five cell lines. It was observed that the lipoconjugates of caffeic acid, sinapic acid, ferulic acid, and coumaric acid displayed anticancer and anti-oxidant properties. The anticancer properties of these derivatives have been assessed by their IC50 inhibitory values in the proliferation of MDA-MB231, SKOV3, MCF7, DU 145 and HepG2 cancer cell lines.

Graphene quantum dots from graphite by liquid exfoliation showing excitation-independent emission, fluorescence upconversion and delayed fluorescence.

Facile synthesis of 2-10 nm-sized graphene quantum dots (GQDs) from graphite powder by organic solvent-assisted liquid exfoliation using a sonochemical method is reported in this study. Synthesized GQDs are well dispersed in organic solvents like ethyl acetoacetate (EAA), dimethyl formamide (DMF) and also in water. MALDI-TOF mass spectrometry reveals its selective mass fragmentation. Detailed characterizations by various techniques like X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and high resolution transmission electron microscopy (HRTEM) confirm the formation of disordered, functional GQDs. Density functional theory (DFT) calculation confirms HOMO-LUMO energy gap variation with changing size and functionalities. Photoluminescence (PL) properties of as-prepared GQDs were studied in detail. The ensemble studies of GQDs showed excellent photoluminescence properties comprising normal and upconverted fluorescence, delayed fluorescence and room-temperature phosphorescence. PL decay dynamics of GQDs has been explored using time-correlated single-photon technique (TCSPC) as well as femtosecond fluorescence upconversion technique. In vitro cytotoxicity study reveals its biocompatibility and high cell viability (>91%) even at high concentration (400 µg mL(-1)) of GQDs in Chinese Hamster Ovary (CHO) cells.