In-silico identification and exploration of small molecule coumarin-1,2,3-triazole hybrids as potential EGFR inhibitors for targeting lung cancer.

Globally, lung cancer is a significant public health concern due to its role as the leading cause of cancer-related mortalities. The promising target of EGFR for lung cancer treatment has been identified, providing a potential avenue for more effective therapies. The purpose of the study was to design a library of 1843 coumarin-1,2,3-triazole hybrids and screen them based on a designed pharmacophore to identify potential inhibitors targeting EGFR in lung cancer with minimum or no side effects. Pharmacophore-based screening was carried out and 60 hits were obtained. To gain a better understanding of the binding interactions between the compounds and the targeted receptor, molecular docking was conducted on the 60 screened compounds. In-silico ADME and toxicity studies were also conducted to assess the drug-likeness and safety of the identified compounds. The results indicated that coumarin-1,2,3-triazole hybrids COUM-0849, COUM-0935, COUM-0414, COUM-1335, COUM-0276, and COUM-0484 exhibit dock score of - 10.2, - 10.2, - 10.1, - 10.1, - 10, - 10 while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of EGFR, indicating their potential as inhibitors. The in-silico ADME and toxicity studies showed that the compounds had favorable drug-likeness properties and low toxicity, further supporting their potential as therapeutic agents. Finally, we performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of coumarin-1,2,3-triazole hybrids as promising EGFR inhibitors for the management of lung cancer.

Regulating the Anode Corrosion by a Tryptophan Derivative for Alkaline Al-Air Batteries.

Screening a green corrosion inhibitor that can prevent Al anode corrosion and enhance the battery performance is highly significant for developing next-generation Al-air batteries. This work explores the non-toxic, environmentally safe, and nitrogen-rich amino acid derivative, N(α)-Boc-l-tryptophan (BCTO), as a green corrosion inhibitor for Al anodes. Our results confirm that BCTO has an excellent corrosion inhibition effect for the Al-5052 alloy in 4 M NaOH solution. An optimum inhibitor addition (2 mM) has increased the Al-air battery performance; the corrosion inhibition efficiency was 68.2%, and the anode utilization efficiency reached 92.0%. The capacity and energy density values increased from 990.10 mA h g-1 and 1317.23 W h kg-1 of the uninhibited system to 2739.70 mA h g-1 and 3723.53 W h kg-1 for the 2 mM BCTO added system. The adsorption behavior of BCTO on the Al-5052 surface was further explored by theoretical calculations. This work paves the way for constructing durable Al-air batteries through an electrolyte regulation strategy.

The broad-spectrum antiviral recommendations for drug discovery against COVID-19.

Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.HighlightsCOVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.

First-principles study of electronic, optical, and thermoelectric properties of KMCuS3 (M = Th and Sm) quaternary chalcogenides.

Copper-based quaternary chalcogenides are considered as intriguing material systems in terms of their remarkable optoelectronic and thermoelectric properties. Here we investigated the light interaction and electronic transport properties of novel KMCuS3 (M = Th, Sm) materials. Advanced computations based on density functional theory were used for these calculations. The PBE-GGA scheme predicted band gaps for the KSmCuS3 and KmThCuS3 were 0.61, and 2.03 eV, respectively. While the TB-mBJ computed band gap values for KSmCuS3 and KThCuS3 were 0.91, and 2.39 eV, respectively. A direct band gap nature for both materials was confirmed by identifying the CBM and VBM at the same high symmetry gamma point. The Cu-d, Sm-f, Th-f, and S-p orbitals unified to form the valence band region at the BZ high symmetry point, while the Th-d and Sm-d orbitals formed the conduction band region. Furthermore, linear optical properties such as complex dielectric function components, along with other important optical parameters were computed and explained for possible employment in optoelectronic devices. The considerable thermoelectric characteristics were also predicted, and the incredible outcomes were described, implying that these compounds have potential for thermoelectric applications.

Theoretical investigation of benzodithiophene-based donor molecules in organic solar cells: from structural optimization to performance metrics.

Achieving high power conversion efficiency (PCE) remains a significant challenge in the advancement of organic solar cells (OSCs). In the field of organic photovoltaics (OPVs), considerable progress has been made in optimizing molecular structures to improve the PCE. However, innovative material design strategies specifically aimed at enhancing PCE are still needed. Here, we have designed BDTS-2DPP-based molecules and propose a molecular design approach to develop donor materials that can significantly improve the PCE of OSCs. Density functional theory (DFT) and time-dependent DFT (TD-DFT) methods have been adopted in both gas and solvent phases. Our newly designed molecule M1 shows the highest absorption value (λ max = 846 nm), highest electron reorganization energy (λ e = 0.18 eV), and the lowest energy gap (E g = 1.81 eV) among all the designed molecules. M1 molecule also exhibits the highest dipole moment in both gas (10.62 D) and solvent phase (13.62 D), and their ground and excited state dipole moment difference is also higher (µ e - µ g = 2.99 D), which enhances its separation to make it a suitable candidate for charge transfer between HOMO-LUMO (97%). Newly designed molecule M3 is observed to have the highest voltage when the current is zero (V oc = 1.15 V) highest PCE value (21.90%) and highest fill factor (FF) value (89.42%). The lowest excitation binding energy is estimated by newly designed molecule M2 (E b = 0.30 eV), which indicates a higher rate of dissociation during the excitation as observed in transition density matrix (TDM) plots. Utilizing electron density difference maps, the newly designed molecules in dichloromethane solvent exhibited consistent intramolecular charge transfer (ICT). The designed molecules were evaluated against reference molecule R to determine if they exhibit superior optoelectronic capabilities. It is found that all designed molecules (M1-M5) exhibit reduced band gaps, are red-shifted in wavelength in comparison to a reference molecule R, and have remarkable charge motilities in terms of reorganisation energies.

High-performance non-fullerene acceptor-analogues designed from dithienothiophen [3,2-b]-pyrrolobenzothiadiazole (TPBT) donor materials.

CONTEXT: Density functional theory (DFT) method was employed to investigate the electronic structure properties, excited state dynamics, charge transfer, and photovoltaic potential of benzo [1,2,5] thiadiazole fused to 3,7-dimethyl-3a,6,7,7b-tetrahydro-5H-thieno[2',3':4,5]thieno[3,2-b]pyrrole to form 3,9,12,13-tetramethyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2″,3″:4,5]pyrrolo[3.2-g]thieno[2',3':4,5]thieno[3,2-b]indole as the acceptor (A), bridge with thiophene as π-spacer to the donor moieties (D) which are 2,3-dihydrobenzo [b]thiophene-6-carboxylic acid (M4) and functionalized R, M1, M2, M3, and M5 to give a D-π-A-π-D. Here is the reverse combination for our molecules: the A-π-D-π-A type of chromophore configuration. It is also observed that tuning the dono-bridge configuration significantly increases the ease of charge transfer as the energy gap decreases in the order of 1.29 eV in M4 < 1.59 eV in M3 < 1.67 eV < 1.99 in M2 and 2.06 eV. The reorganization energy (RE) of M3 (0.0031) and M5 (0.0031) indicates an increase in the order of M3 > M5 > R > M2 > M4 > M1. The HOMO-LUMO indicates that the reactivity decreased, while the stability increased for the reference R at 0.990 eV, compared to the designed molecules M1-M5, with M1 being the least stable at 0.970 eV, while M4 exhibited the highest stability at 1.550 eV. The stability of the designed molecule decreased in the order of M4:1.550 > M3:1.257 > M5:1.197 > M2:1.010 > M1:0.970. Therefore, all results point to the electron-deficient core as an effective end-capped electron acceptor in M1-M5 compounds. As the ideal pair for successfully optimizing optoelectronic properties by reducing the HOMO-LUMO energy levels, reorganization energy, and binding energy and enhancing the absorption maximum and open-circuit voltage values in these designed molecules. METHODS: DFT and TDDFT calculations were performed with Gaussian 16 program. The modelled compounds were optimized fully using the CAM-B3LYP, WB97XD, B3LYP, and MPW1PW91 functionals with the 6-31 G (d,p) basis set. The graphs for the density of states were plotted using the PyMOlyze software. Other molecular properties like the transition density matrix (TDM) and electron density difference maps (EDD) were rendered via the Multiwfn software.

In-silico design, pharmacophore-based screening, and molecular docking studies reveal that benzimidazole-1,2,3-triazole hybrids as novel EGFR inhibitors targeting lung cancer.

Lung cancer is a complex and heterogeneous disease, which has been associated with various molecular alterations, including the overexpression and mutations of the epidermal growth factor receptor (EGFR). In this study, designed a library of 1843 benzimidazole-1,2,3-triazole hybrids and carried out pharmacophore-based screening to identify potential EGFR inhibitors. The 164 compounds were further evaluated using molecular docking and molecular dynamics simulations to understand the binding interactions between the compounds and the receptor. In-si-lico ADME and toxicity studies were also conducted to assess the drug-likeness and safety of the identified compounds. The results of this study indicate that benzimidazole-1,2,3-triazole hybrids BENZI-0660, BENZI-0125, BENZI-0279, BENZI-0415, BENZI-0437, and BENZI-1110 exhibit dock scores of -9.7, -9.6, -9.6, -9.6, -9.6, -9.6 while referencing molecule -7.9 kcal/mol for EGFR (PDB ID: 4HJO), respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of EGFR, indicating their potential as inhibitors. The in-silico ADME and toxicity studies showed that the compounds had favorable drug-likeness properties and low toxicity, further supporting their potential as therapeutic agents. Finally, performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of benzimidazole-1,2,3-triazole hybrids as promising EGFR inhibitors for the treatment of lung cancer. This research opens up a new avenue for the discovery and development of potent and selective EGFR inhibitors for the treatment of lung cancer.Communicated by Ramaswamy H. Sarma.

Increasing the Photovoltaic Power of the Organic Solar Cells by Structural Modification of the R-P2F-Based Materials.

CONTEXT: The present study aims to improve the performance of optoelectronics and photovoltaics by constructing an acceptor-donor-acceptor (A-D-A) molecule with a fullerene-free acceptor moiety. The study utilizes malononitrile and selenidazole derivatives to tailor the molecule for enhanced photovoltaic abilities. The study analyzes molecular properties and parameters like charge density, charge transport, UV absorption spectra, exciton binding energies, and electron density difference maps to determine the effectiveness of the tailored derivatives. METHODS: To optimize the geometric structures, the study used four different functionals (B3LYP, CAM-B3LYP, MPW1PW91, and É·B97XD) along with a double zeta valence basis set 6-31G(d, p) basis set. The study compared the results of the tailored derivatives with a reference molecule (R-P2F) to determine improvements in performance. The light harvesting efficiency of the molecules was analyzed by performing simulations in the gas and solvent phases (chloroform) based on the spectral overlap between the solar irradiance and the absorption spectra of the molecules. The open-circuit voltage (VOC) of each molecule was also analyzed, representing the maximum voltage that can be obtained from the cell under illuminated conditions. The findings indicated that the M1-P2F designed derivative is a more effective, with energy gap of 2.14 eV, and suitable candidate for non-fullerene organic solar cell application, based on various analyses such as power conversion efficiency, quantum chemical reactivity parameters, and electronic features.

In-silico identification of small molecule benzofuran-1,2,3-triazole hybrids as potential inhibitors targeting EGFR in lung cancer via ligand-based pharmacophore modeling and molecular docking studies.

Lung cancer is one of the most common and deadly types of cancer worldwide, and the epidermal growth factor receptor (EGFR) has emerged as a promising therapeutic target for the treatment of this disease. In this study, we designed a library of 1840 benzofuran-1,2,3-triazole hybrids and conducted pharmacophore-based screening to identify potential EGFR inhibitors. The 20 identified compounds were further evaluated using molecular docking and molecular dynamics simulations to understand their binding interactions with the EGFR receptor. In-silico ADME and toxicity studies were also performed to assess their drug-likeness and safety profiles. The results of this study showed the benzofuran-1,2,3-triazole hybrids BENZ-0454, BENZ-0143, BENZ-1292, BENZ-0335, BENZ-0332, and BENZ-1070 dock score of - 10.2, - 10, - 9.9, - 9.8, - 9.7, - 9.6, while reference molecule - 7.9 kcal/mol for EGFR (PDB ID: 4HJO) respectively. The molecular docking and molecular dynamics simulations revealed that the identified compounds formed stable interactions with the active site of the receptor, indicating their potential as inhibitors. The in-silico ADME and toxicity studies suggested that the compounds had good pharmacokinetic and safety profiles, further supporting their potential as therapeutic agents. Finally, performed DFT studies on the best-selected ligands to gain further insights into their electronic properties. The findings of this study provide important insights into the potential of benzofuran-1,2,3-triazole hybrids as promising EGFR inhibitors for the treatment of lung cancer. Overall, this study provides a valuable starting point for the development of novel EGFR inhibitors with improved efficacy and safety profiles. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00157-1.

An extension of electron acceptor sites around Thiazolothiazole unit for evaluation of large power conversion efficiency: A theoretical insight.

Small organic solar cells containing thiazolothiazole unit as an electron acceptor for solution processed bulk heterojunction (BHJ) small donor-acceptor-donor (D-A-D) type materials have been designed and studied theoretically with state-of-the-art density functional theory and time-dependent density functional theory (TD-DFT) for reliable estimation of their excited state and charge transfer photophysical characteristics for estimating their power conversion efficiencies. The suggested possible synthetic routes with complete reaction information have been also provided for synthesis. The electron acceptor sites around the thiazolothiazole unit have been enlarged by introducing different strong electron withdrawing groups and checked their effects on the voltages (VOC) and fill factor (FF) which are the two main parameters directly influences on power conversion efficiencies. Out of five theoretically studied molecules, the experimental reported data of TT-TTPA (Thiazolothiazole-thiaophene triphenyl amine) has been compared with four designed molecules and concluded that extension of acceptor sites significantly contributed towards the better charge transport properties of electron and hole.

Impact of Facebook and Newspaper Advertising on Sales: A Comparative Study of Online and Print Media.

Marketing means the strategies and tactics an organization undertakes for attracting consumers to promote the buying or selling of a product or service. Active marketing is about receiving messages from potential buyers to create ways to influence their purchasing decisions. Advertising is one of the most prominent marketing strategies to promote products to consumers. It is well known that advertisement has a significant impact on the sale of certain goods or services. In this paper, we consider two mediums of advertisement, such as Facebook (which is an online medium) and Newspaper (which is a printed medium). We consider a dataset representing the advertising budget (in hundreds of US dollars) of an electronic company and the sales of that company. We apply the quantitative research approach, and the data which are used in this research are secondary data. For analysis purposes, we consider a statistical tool called simple linear regression modeling. To check the significance of the advertising on sale, definite statistical tests are applied. Based on the findings of this research, it is observed that advertising has a significant impact on sales. It is also showed that spending money on advertising through Facebook has better sales than newspapers. The finding of this research shows that the use of computer-based technologies and online mediums has a brighter future for advertising. Furthermore, a new statistical model is introduced using the Z family approach. The proposed model is very interesting and possesses heavy-tailed properties. Finally, the applicability of the proposed model is illustrated by considering the financial dataset.