Design of Metal Free Fluorescent Pyridine Dyes Anchored on Cadmium Sulfide Nanowires: Optical, Electrochemical and Photovoltaic Applications.

Through a facile two-step synthetic procedure, three metal-free organic dyes having D-π-A kind of structure, belonging to chalcone family have been designed, produced and anchored on one dimensional cadmium sulfide nanowires (1D CdS NWs) to serve as a light energy harvester through dye-sensitized solar cells (DSSC) assembly. In order to anchor dye on CdS NWs nano-network, solution chemistry has been used in an easy and effective manner. The sensitizing capability of synthesized materials has been evaluated using optical and electrochemical studies, density functional theory (DFT) simulations, and photovoltaic performances. In line with a detailed analysis of fabricated Dye sensitized solar cells containing T4PC a photovoltaic efficiency yields 4.35 times (0.487%) more than that of bare CdS NWs (0.112%), while the other devices having T3PC and T2PC have shown 3.0 (0.338%) and 2.40 (0.273%) times greater photovoltaic efficiencies, respectively under standard light illumination. The obtained results offer solid evidence in favour of boosting external quantum efficiency (EQE) and reflect good agreement with the optical studies.

Design and Synthesis of Novel Fluorescent 2-(aryloxy)-3-(4,5-diaryl)-1H-imidazol-2-yl)quinolines: Solvatochromic, DFT, TD-DFT Studies, COX-1 and COX-2 Inhibition and Antioxidant Properties.

The present work focuses on the synthesis of novel heterocycles 2-(aryloxy)-3-(4,5-diaryl-1H-imidazol-2-yl)quinolines (6k-v) by an effective condensation reaction. These molecules exhibited fluorescent properties and hence for the proper understanding of their optical behavior and quantum yields, solvatochromic studies have been carried out. Further, frontier molecular orbitals, molecular electrostatic potential (MEP), and geometrical structure optimization have been investigated using the B3LYP/6-311G ++ (d, p) method. The energy gap between the HOMO, LUMO of the optical and energy band gap is determined by DFT and UV-visible spectra for TD-DFT studies are done. The screening of these compounds for in vitro COX-1 and COX-2 inhibition and DPPH free radical scavenging ability assays produced promising results. The binding interactions of these molecules against the COX-2 enzyme (PDB: 5IKR) were validated by docking studies.

Exploration of Coumarin Derivative: Experimental and Computational Modeling for Dipole Moment Estimation and Thermal Sensing Application.

The Optical properties of the FBTC (1-((4-((5-chlorobenzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-3H-benzo[f]chromen-3-one) molecule were studied experimentally and theoretically. The spectra of absorption and fluorescence were recorded in various solvents to explore their Solvatochromic behavior and dipole moment at room temperature. To determine the ground and excited state of dipole moment experimentally and theoretically, we employed different Solvatochromic techniques, including microscopic solvent polarity functions developed by Lippert, Bakhshiev, Kawaski-Chamma-Viallet, and Reichardt's, as well as density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods. The stability of the excited state dipole moment in FBTC is higher. Using prime functional, FBTC was optimized in its ground state, and its HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital), energies were estimated. These values were then compared with those obtained through cyclic voltammetry. Based on the HOMO and LUMO values given, we calculated the global reactivity parameter and energy gap, which was found to be low at 3.77 eV. This study also includes an estimation of electron absorption energies and oscillator strength. Natural population analysis (NPA), Milliken atomic charge, and molecular electrostatic potential (MESP) map are correlated. In addition, FBTC exhibited exceptional physiological temperature sensing behaviour from 20 °C -65 °C with high relative sensitivity and firm stability. Hence these results confirm that FBTC is a potential candidate for photonic devices and it's also applicable in optical temperature sensing.

Pretreatment hematological parameters as predictors of tumor granulocyte-colony-stimulating factor expression in patients of head-and-neck squamous cell carcinoma.

Background: Tumor secreting granulocyte-colony-stimulating factor (G-CSF) and/or G-CSF therapy has been documented as a poor prognostic factor. Tumor G-CSF study is a relatively costly and sparsely available investigation. Therefore, this study was undertaken to predict tumor G-CSF score from pretreatment hematological parameters (PTHP) in patients of head-and-neck squamous cell carcinoma (HNSCC). Materials and Methods: This pilot study was performed after institutional ethics committee approval. Consecutive nonmetastatic HNSCC patients of oral cavity, oropharynx, hypopharynx, and larynx registered from February to December 2019 were analyzed. Patients whose PTHP and formalin-fixed-paraffin-embedded tissue were available, were included. PTHP (absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute lymphocyte count [ALC], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) done before any active oncology treatment, were noted. A semiquantitative tumor G-CSF score was calculated. Tumor G-CSF score and PTHP were correlated with clinicopathological factors. Statistical analysis was performed using SYSTAT version 12. Results: Data of 47 eligible patients were analyzed. The median age at presentation was 60 years. The male-to-female ratio was 43:4. The most common head-and-neck subsite was oropharynx (31.92%), and majority of patients presented with Stage IVA disease (51.1%). Higher tumor G-CSF score was significantly associated with a higher T-stage (P = 0.013). Tumor G-CSF score was directly proportional to ANC, AMC, and ALC while it was inversely proportional to NLR and PLR. Regression equations to predict the tumor G-CSF score when PTHP are known, were determined. Conclusions: PTHP can predict the tumor G-CSF score which may guide G-CSF-directed therapy. Future studies with large number of patients are needed to elucidate its clinical use.

Novel jointured green synthesis of chitosan­silver nanocomposite: An approach towards reduction of nitroarenes, anti-proliferative, wound healing and antioxidant applications.

Here we present the simple green synthesis of chitosan­silver nanocomposite (CS-Ag NC) by employing kiwi fruit juice as reducing agent. The structure, morphology, and composition of CS-Ag NC were determined using characterization techniques such as XRD, SEM-EDX, UV-visible, FT-IR, particle size, and zeta potential. The prepared CS-Ag nanocomposite was effectively used as catalyst in the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4 as reductant, in aqueous medium at room temperature. The toxicity of CS-Ag NC was assessed on Normal (L929) cell line, Lung cancer (A549) cell line and Oral cancer (KB-3-1) cell line and their respective IC50values observed were 83.52 µg/mL, 66.74 µg/mL and 75.11 µg/mL. The CS-Ag NC displayed significant cytotoxic activity and the cell viability percentage for normal, lung and oral cancer cell lines were found to be 42.87 ± 0.0060, 31.28 ± 0.0045 and 35.90 ± 0.0065 respectively. Stronger cell migration was exemplified by CS-Ag NC and the percentage of wound closure (97.92%) was substantially identical to that of the standard drug ascorbic acid (99.27%). Further CS-Ag nanocomposite was subjected for in vitro antioxidant activity.

S-BIRD: A Novel Critical Multi-Class Imagery Dataset for Sewer Monitoring and Maintenance Systems.

Computer vision in consideration of automated and robotic systems has come up as a steady and robust platform in sewer maintenance and cleaning tasks. The AI revolution has enhanced the ability of computer vision and is being used to detect problems with underground sewer pipes, such as blockages and damages. A large amount of appropriate, validated, and labeled imagery data is always a key requirement for learning AI-based detection models to generate the desired outcomes. In this paper, a new imagery dataset S-BIRD (Sewer-Blockages Imagery Recognition Dataset) is presented to draw attention to the predominant sewers' blockages issue caused by grease, plastic and tree roots. The need for the S-BIRD dataset and various parameters such as its strength, performance, consistency and feasibility have been considered and analyzed for real-time detection tasks. The YOLOX object detection model has been trained to prove the consistency and viability of the S-BIRD dataset. It also specified how the presented dataset will be used in an embedded vision-based robotic system to detect and remove sewer blockages in real-time. The outcomes of an individual survey conducted at a typical mid-size city in a developing country, Pune, India, give ground for the necessity of the presented work.

Experimental and Theoretical Spectroscopic Investigation on Coumarin Based Derivatives for Non-Linear Optoelectronics Application.

The spectral properties of MBTC (4-((4-((Benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-7-methoxy-2H-chromen-2-one), CBTC (4-((4(((5Chlorobenzo[d]oxazol-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)methyl)-2H-benzo[h]chromen-2-one) and TBTC (4-((4-((Benzo[d]oxazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)methyl)6(tertbutyl)2Hchromen-2-one) were studied in series of solvents with different polarity at room temperature to explore their solvatochromic effect and dipole moment. Stokes shift revealed a bathochromic shift with varying solvent polarity for all molecules which implies π-π*transition. The ground state and excited state dipole moment of the molecules are calculated experimentally using salvatochromic methods like Lippert-Mataga, Bakhshiev, Kawaski-chamma-viallet, and Reichardt's microscopic solvent polarity functions and computationally by density functional theory (DFT) method. It is observed that the excited state dipole moment is higher than the ground state so synthesized molecules are more polar in the excited state than in the ground state. Using the DFT method HOMO and LUMO energy values were obtained and compared with values obtained by the cyclic voltammetry. Using the values of HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) we have estimated energy gap, chemical hardness (ɳ), chemical softness (s), ionization potential (IP), electron affinity (EA), electronegativity (χ), electrophilicity (ω), and chemical potential (µ) of the molecules were estimated. The energy gap of MBTC, CBTC, and TBTC were found to be low, that is 3.861 eV, 3.822 eV, and 3.801 eV respectively, this indicates molecules are more reactive and it has the easiest π-π* transition. Further electrophilic and nucleophilic sites were figured out using molecular electrostatic potential (MESP) which is useful in photochemical reactions. Hence the quantum chemical calculation and spectroscopic properties of the molecules can give a better understanding of their use in an optoelectronic device.

Coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones: Synthesis, glucose uptake activity and cytotoxic evaluation.

Thiazolidinedione (TZD) based medications have demonstrated to enhance the insulin sensitivity control, hyperglycemia, and lipid metabolism in patients with type 2 diabetes. Hence, in this study, a new series of novel coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones (TZD1-TZD18) were synthesized via copper (I)-catalyzed azide-alkyne cycloaddition "Click Chemistry". The synthesized compounds were evaluated for their glucose uptake assay and in vitro cytotoxicity against HEK-293 (human embryonic kidney) cells which were compared with the standard drug Pioglitazone. Further, molecular docking analysis of these compounds was carried out to explain the in vitro results with PPARγ (PDB ID: 3CS8) and to better understand the bonding interactions with the target protein. The outcomes of in vitro assessment, molecular docking, and pharmacokinetics of the title compounds were revealed to be highly correlated. Interestingly, the compounds TZD4, TZD10, TZD14 and TZD16 were most efficient in lowering the blood glucose level compared with standard drug.

Utility and diagnostic test properties of pulmonary and cardiovascular point of care ultra-sonography (POCUS) in COVID-19 patients admitted to critical care unit.

Background: We conducted this study to assess the diagnostic test properties of point of care ultrasonography (POCUS) of lung and cardiovascular system in prediction of mortality in COVID-19 patients. Methods: This is a cross-sectional study of 178 Covid-19 patients; POCUS was performed within one hour of admission to the ICU. We estimated sensitivity, specificity, positive predictive value, negative predictive value for prediction of mortality. Results: The mean (SD) age of these patients was 57.3 (12.8) years. The findings were on cardiac ultrasonography were: mild pericardial effusion (45%), chamber dilatation (15%), hypokinesia (11%), and low ejection fraction (8%). In our study, 30 patients (17%) had died. A cut-off score of > to 13 (for lung ultrasound score [LUS]) had high sensitivity for mortality (93.3%, 95% CI: 77.9-99.2%). However, low ejection fraction (92.3%, 95% CI: 86,6-96.1%), and thrombosis in either vein (96.5%, 95% CI: 92.0-98.9%) were specific for mortality. A combination of LUS > =13 or low ejection fraction or thrombosis or spontaneous echo contrast (slow flow) improved sensitivity for mortality to 96.7% (95% CI: 82.8-99.9%). The agreement between LUS of > =13 and CT score of moderate/severe was 85.7% (95% CI: 62.8-100%). The interrater agreement between these two parameters was 0.82 (95% CI: 0.68, 0.97). Conclusions: Multi-organ POCUS is effective in diagnosis, prognosis, and management of COVID-19 patients. Rather than just lung ultrasound, clinicians should use multiorgan POCUS for early identification of severe lung involvement and thrombotic changes; it may help reduce mortality in these patients.

Tumor Cell-Specific Retention and Photodynamic Action of Erlotinib-Pyropheophorbide Conjugates.

To enhance uptake of photosensitizers by epithelial tumor cells by targeting these to EGFR, pyropheophorbide derivatives were synthesized that had erlotinib attached to different positions on the macrocycle. Although the addition of erlotinib reduced cellular uptake, several compounds showed prolonged cellular retention and maintained photodynamic efficacy. The aim of this study was to identify whether erlotinib moiety assists in tumor targeting through interaction with EGFR and whether this interaction inhibits EGFR kinase activity. The activity of the conjugates was analyzed in primary cultures of human head and neck tumor cells with high-level expression of EGFR, and in human carcinomas grown as xenografts in mice. Uptake of erlotinib conjugates did not correlate with cellular expression of EGFR and none of the compounds exerted EGFR-inhibitory activity. One derivative with erlotinib at position 3, PS-10, displayed enhanced tumor cell-specific retention in mitochondria/ER and improved PDT efficacy in a subset of tumor cases. Moreover, upon treatment of the conjugates with therapeutic light, EGFR-inhibitory activity was recovered that attenuated EGFR signal-dependent tumor cell proliferation. This finding suggests that tumor cell-specific deposition of erlotinib-pyropheophorbides, followed by light triggered release of EGFR-inhibitory activity, may improve photodynamic therapy by attenuating tumor growth that is dependent on EGFR-derived signals.

Metastatic malignant melanoma: A case of metastasis from foot to mandibular anterior region.

Metastatic malignant melanoma (MMM) of the oral cavity is extremely rare which generally presents in the setting of disseminated disease and have extremely poor prognosis. The most common site for MMM in the oral cavity is tongue followed by buccal mucosa for soft-tissue lesions and posterior mandible for bone involving lesions. Primary tumor sites of oral MMM are usually cutaneous lesions of the trunk, head and neck, limbs, and nasal septum mucosa. Patients bearing this diagnosis face median survival time of approximately 9 months with a probability of surviving 5 years after the initial presentation is <5%; hence, an early detection and treatment for the primary and metastatic lesion is crucial. Here, we present an unusual case of MMM of oral cavity involving gingiva and alveolar bone of the mandibular anterior region metastasizing from a primary lesion on the foot.

Tumor-Avid 3-(1'-Hexyloxy)ethyl-3-devinylpyrpyropheophorbide-a (HPPH)-3Gd(III)tetraxetan (DOTA) Conjugate Defines Primary Tumors and Metastases.

3-(1'-Hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll a derivative currently undergoing human clinical trials, was conjugated with mono-, di-, and tri-Gd(III)tetraxetan (DOTA) moieties. The T1/T2 relaxivity and in vitro PDT efficacy of these conjugates were determined. The tumor specificity of the most promising conjugate was also investigated at various time points in mice and rats bearing colon tumors, as well as rabbits bearing widespread metastases from VX2 systemic arterial disseminated metastases. All the conjugates showed significant T1 and T2 relaxivities. However, the conjugate containing 3-Gd(III)-aminoethylamido-DOTA at position 17 of HPPH demonstrated great potential for tumor imaging by both MR and fluorescence while maintaining its PDT efficacy. At an MR imaging dose (10 µmol/kg), HPPH-3Gd(III)DOTA did not cause any significant organ toxicity in mice, indicating its potential as a cancer imaging (MR and fluorescence) agent with an option to treat cancer by photodynamic therapy (PDT).

Calcium Ion-Sodium Alginate-Piperine-Based Microspheres: Evidence of Enhanced Encapsulation Efficiency, Bio-Adhesion, Controlled Delivery, and Oral Bioavailability of Isoniazid.

Isoniazid (INH) is a first-line chemotherapeutic drug employed in the management of tuberculosis. However, its extensive first-pass metabolism, short-life life, and low oral bioavailability confined its medical application. Therefore, the calcium ion-alginate-piperine microspheres (INH-CaSP Ms) was prepared to enhance encapsulation efficiency, controlled delivery, and oral bioavailability of INH. The INH-CaSP Ms was developed using a modified emulsification method and optimized via Box-Behnken design (BBD). Optimized INH-CaSP Ms were characterized for encapsulation efficiency, differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), bio-adhesion, in vitro dissolution, ex vivo permeation, and oral bioavailability studies. Characterization studies confirmed the formation of microspheres. The INH-CaSP Ms showed spherical microspheres with enhanced encapsulation efficiency (~ 93.03 ± 1.54% w/w). The optimized INH-CaSP Ms exhibited higher bio-adhesion around (~ 81.41 ± 1.31%). The INH-CaSP Ms enhanced the dissolution rate of INH (~ 57%) compared to pure INH (~ 57%) and INH-SA Ms (~ 81%) in simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.4). The same formulations improved the permeation rate of INH (~ 90%) compared to pure INH (~ 55%) and INH-SA Ms (~ 80%). The oral bioavailability results indicated that INH-CaSP Ms appreciably improved the oral bioavailability of INH via increasing the Cmax, Tmax, t1/2, and AUC parameters compared to pure INH. The study demonstrates that the development of INH-CaSP Ms via cross-linked coordinate bond interaction between divalent cation calcium ion-alginate complex and anion piperine bio-enhancer is an effective approach for enhancing the encapsulation efficiency, bio-adhesion, controlled release, and oral bioavailability of INH.

WELPSA: A natural catalyst of alkali and alkaline earth metals for the facile synthesis of tetrahydrobenzo[b]pyrans and pyrano[2,3-d]pyrimidinones as inhibitors of SARS-CoV-2.

Since 2019, the infection of SARS-CoV-2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3-d]pyrimidinones as SARS-CoV-2 inhibitors via three-component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. Lemon peel from juice factory waste, namely, lemon (Citrus limon), sweet lemon (C. limetta), and Kaffir lime or Citron (C. hystrix), effectually utilized to obtain WELPSA, WESLPSA, and WEKLPSA, respectively, for the synthesis of title compounds. The catalyst was characterized by scanning electron microscope (SEM) and energy-dispersive x-ray spectroscopy (EDX). The concentration of sodium, potassium, calcium, and magnesium in the catalyst (WELPSA) was determined using atomic absorption spectrometry (AAS). The current approach manifests numerous notable advantages that include ease of preparation, handling and benignity of the catalyst, low cost, green reaction conditions, facile workup, excellent yields (93%-97%) with extreme purity, and recyclability of the catalyst. Compounds were docked on the crystal structure of SARS-CoV-2 (PDB: 6M3M). The consensus score obtained in the range 2.47-4.63 suggests that docking study was optimistic indicating the summary of all forces of interaction between ligands and the protein.

Increased frequency of pneumothorax and pneumomediastinum in COVID-19 patients admitted in the ICU: A multicentre study from Mumbai, India.

BACKGROUND: There are limited data regarding the incidence of pneumothorax in COVID-19 patients as well as the impact of the same on patient outcomes. METHODS: A retrospective review of the medical records at three large tertiary care hospitals in Mumbai was performed to identify patients hospitalised with COVID-19 from March 2020 to October 2020. The presence of pneumothorax and/or pneumomediastinum was noted when chest radiographs or CT scans were performed. Demographic and clinical characteristics of patients who developed air leak were recorded. RESULTS: 4,906 patients with COVID-19 were admitted, with 1,324 (27%) having severe COVID-19 disease. The overall incidence of pneumothorax and/or pneumomediastinum in patients with severe disease was 3.2% (42/1,324). Eighteen patients had pneumothorax, 16 had pneumomediastinum and 8 patients had both. Fourteen patients (33.3%) developed this complication breathing spontaneously, 28 patients (66.6%) developed it during mechanical ventilation. Overall mortality in this cohort was 74%, compared with 17% in the COVID-19 patients without pneumothorax (p<0.001). CONCLUSIONS: Our study demonstrates that air leaks occur with a higher frequency in patients with COVID-19 than in other ICU patients. When present, such air leaks contributed to poor outcomes with almost 74% mortality rates in these patients.

Green synthesis of therapeutically active 1,3,4-oxadiazoles as antioxidants, selective COX-2 inhibitors and their in silico studies.

A modest, competent and green synthetic procedure for novel coumarinyl-1,3,4-oxadiazolyl-2-mercaptobenzoxazoles 8i-t has been reported. Analysis of the docked (PDB ID: 5IKR; A-Chain) poses of the compounds illustrated that they adopt identical conformations to the extremely selective COX-2 inhibitor. The biological outcomes as well as computational study suggested that the compounds originated to have elevated resemblance towards COX-2 enzyme than COX-1. The compounds 8i, 8l, 8q, 8r, 8s and 8t emerged as most potent and selective COX-2 inhibitors in contrast with Mefenamic acid. The selectivity index of 8l, 8n and 8r was respectively found to be 33.95, 20.25 and 24.98 which manifested their high selectivity against COX-2. Interestingly, the compounds which were active as COX-2 inhibitors were also active as antioxidant agents.

Chiral Alkyl Groups at Position 3(1') of Pyropheophorbide-a Specify Uptake and Retention by Tumor Cells and Are Essential for Effective Photodynamic Therapy.

To investigate the importance of the chirality and precise structure at position 3(1') of pyropheophorbide-a for tumor cell specificity and photodynamic therapy (PDT), a series of photosensitizers (PSs) was synthesized: (a) with and without chirality at position 3(1'), (b) alkyl ether chain with a variable number of chiral centers, (c) hexyl ether versus thioether side chain, and (d) methyl ester versus carboxylic acid group at position 172. The cellular uptake and specificity were defined in human lung and head/neck cancer cells. PSs without a chiral center and with an alkyl chain or thioether functionalities showed limited uptake and PDT efficacy. Replacing the methyl group at the chiral center with a propyl group or introducing an additional chiral center improved cellular retention and tumor cell specificity. Replacing the carboxylic acid with methyl ester at position 172 lowered cellular uptake and PDT efficacy. A direct correlation between the PS uptake in vitro and in vivo was identified.

Microwave assisted regioselective synthesis of quinoline appended triazoles as potent anti-tubercular and antifungal agents via copper (I) catalyzed cycloaddition.

Quinolin-3-yl-methyl-1,2,3-triazolyl-1,2,4-triazol-3(4H)-ones 8j-v were synthesized by click chemistry as an ultimate tactic where [3 + 2] cycloaddition of azides with terminal alkynes has been evolved. Herein, we are inclined to divulge the implication and prevalence of CuSO4·5H2O and THF/water promoted [3 + 2] cycloaddition reactions. The foremost supremacy of this method are transitory reaction times, facile workup, excellent yields (88-92%) with exorbitant purity and regioselective single product formation both under conventional and microwave method. Docking studies illustrated strong binding interactions with enzyme InhA-D148G (PDB ID: 4DQU) by means of high C-score values. The anti-tubercular and antifungal screening of synthesized compounds proclaimed promising activity. The in vitro and in silico studies imply that these triazoles appended quinolines may acquire the ideal structural prerequisites for auxiliary expansion of novel therapeutic agents.

Synthesis, Tumor Specificity, and Photosensitizing Efficacy of Erlotinib-Conjugated Chlorins and Bacteriochlorins: Identification of a Highly Effective Candidate for Photodynamic Therapy of Cancer.

Erlotinib was covalently linked to 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) and structurally related chlorins and bacteriochlorins at different positions of the tetrapyrrole ring. The functional consequence of each modification was determined by quantifying the uptake and subcellular deposition of the erlotinib conjugates, cellular response to therapeutic light treatment in tissue cultures, and in eliminating of corresponding tumors grown as a xenograft in SCID mice. The experimental human cancer models the established cell lines UMUC3 (bladder), FaDu (hypopharynx), and primary cultures of head and neck tumor cells. The effectiveness of the compounds was compared to that of HPPH. Furthermore, specific functional contribution of the carboxylic acid side group at position 172 and the chiral methyl group at 3(1') to the overall activity of the chimeric compounds was assessed. Among the conjugates investigated, the PS 10 was identified as the most effective candidate for achieving tumor cell-specific accumulation and yielding improved long-term tumor control.

Quinoline Derivative Enhances Human Sperm Motility and Improves the Functional Competence.

In this study, we aimed to explore the beneficial properties of novel quinoline derivatives on human sperm motility and its functional competence. Nine novel quinoline derivatives were screened for their effect on motility in human spermatozoa from normozoospermic ejaculates. Compounds with impressive sperm motility enhancement properties were further assessed for their effect on functional competence of human spermatozoa. To determine the effect on the fertilizing ability of spermatozoa processed with quinoline derivatives and to assess developmental competence of embryos derived, in vitro fertilization (IVF) was performed using mouse model. Among the nine quinoline derivatives, 2 compounds (6MQT and 2,6DQT) exhibited significant enhancement in sperm progressive motility and survival at 24 h. Further, non-significant increase in curvilinear velocity (VCL), straight line velocity (VSL), and amplitude of lateral head displacement (ALH) was observed. Capacitation, intracellular cAMP level and tyrosine phosphorylated sperm proteins were significantly higher in 6MQT (P < 0.05) and 2,6DQT (P < 0.001) compared to control. In vitro fertilization (IVF) experiments using Swiss albino mice revealed that spermatozoa processed with 6MQT had non-significantly higher blastocyst rate and a superior blastocyst quality, while, 2,6DQT resulted in significantly lower blastocyst rate (P < 0.05) compared to control. Quinoline derivative 6MQT has significant motility enhancement property under in vitro conditions. Graphical abstract.