How causality impacts the renewable energy, carbon emissions, and economic growth nexus in the South Caucasus Countries?

Renewable energy is essential for boosting economic expansion and lowering carbon dioxide emission (CO2) to achieve carbon neutrality. This study's objective is to investigate the relationship between the use of renewable energy, economic growth, and CO2 for South Caucasus Countries. For analysis purposes, time series methods were applied on the panel data. Second-generation unit root and cointegration tests were used to test the cross-sectional dependence. Afterward, panel causality and panel VAR techniques were performed to examine the relationship between the variables. Based on feedback hypothesis, results of our causality analysis revealed a bidirectional causality relationship between growth and renewable energy consumption. Moreover, we revealed unidirectional causality from CO2 to renewable energy and from growth to CO2 emission. We also found that the effect of a shock in renewable energy on growth is increasing, and on CO2, it is decreasing implying that renewable energy consumption will trigger growth and have a reducing effect on CO2 emissions. We portrayed significant workable implications for policymakers, regulation bodies, companies, stakeholders, and managers. Results from this study should be extrapolated with caution since their applicability is limited to the South Caucasus Countries. In addition, the research heavily depends on summaries, which may obscure regional differences. In the future, researchers may want to dig deeper into the data and examine the subtle effect of renewable energy policy nationally. Moreover, including socio-economic aspects and technical improvements in the research might give a more thorough picture of the dynamics at play.

Performance of angle shear connectors for U-shaped steel concrete infilled composite beams.

The current design codes i.e. AISC 360-16, CSA-S16-19, EC-04 etc. provide empirical relationships to estimate the capacity of shear connectors which were developed based on pushout tests of headed studs and channels connectors in exposed type sections. Therefore, these equations may result inaccurate predictions for strength of connectors in infilled-type sections. This study presents a detailed experimental study investigating the performance of angle connectors in composite sections. The testing program consisted two series of pushout tests. A total of 36 specimens were tested, considering the influence of several important parameters i.e. the length (Lc), height (hc), and web-thickness (tw) of angle connector, length of the weld (w) and the direction of shear connector (forward/backward) etc. The tests results demonstrated that with increasing connector height hs, and thickness, the maximum load Pmax and slip δu were increased. The connector direction didn't change much the load-slip behavior. The prediction accuracy of the existing shear capacity models was evaluated by comparing the predictions with experimental results. The current equations were noticed to be highly inconsistent in predicting the shear capacity of angle connectors, especially in case of infilled type sections. When the entire length of connector was taken as the effective length, the models overestimated the shear capacity. While in case when the welding length was taken as effective length in calculations, the models underestimated the shear strength of angle connectors.

Synthesis of hydrazinyl-thiazole ester derivatives, in vitro trypanocidal and leishmanicidal activities.

Aim: To synthesize novel more potent trypanocidal and leishmanicidal agents. Methods: Hantzsch's synthetic strategy was used to synthesize 1,3-thiazole-4-carboxylates and their N-benzylated derivatives. Results: 28 new thiazole-carboxylates and their N-benzylated derivatives were established to test their trypanocidal and leishmanicidal activities. From both series, compounds 3b, 4f, 4g, 4j and 4n exhibited a better or comparable trypanocidal profile to benznidazole. Among all tested compounds, 4n was found to be the most potent and was better than benznidazole. Conclusion: Further variation of substituents around 1,3-thiazole-4-carboxylates and or hydrazinyl moiety may assist in establishing better and more potent trypanocidal and leishmanicidal agents.

Chagas disease and leishmaniasis are neglected tropical diseases. Herein, 28 1,3-thiazoles have been synthesized from thiosemicarbazones in a rapid, efficient and cost-effective manner. In vitro assays were performed against intracellular amastigotes of Trypanosoma cruzi (T. cruzi) and promastigotes and intracellular amastigote forms of Leishmania infantum (L. infantum) and Leishmania amazonensis (L. amazonensis). Some of the 1,3-thiazole-4-carboxylates inhibited the amastigote form of T. cruzi without affecting macrophage viability, compound 4n being the most potent and better than benznidazole. Our synthesized compounds exhibited promising activity against T. cruzi, thus broadening options for scaffold and lead compound optimization. Concerning the leishmanicidal activity, compound 4g was the best prototype in terms of potency and selectivity. Compounds 4g and 3m showed moderate selectivity and potency against intracellular amastigotes of L. amazonensis and L. infantum, respectively.

Effects of long-term proton pump inhibitor use on sexual hormones and sexual and reproductive health in female patients.

PURPOSE: Proton pump inhibitors (PPIs) are widely used to treat a range of gastrointestinal diseases around the world. Long-term use of PPIs has been associated to a variety of undesirable effects. Although short-term therapy has been shown to have little or no effect on endocrine hormone in women, however, its long-term safety has received little attention. We aimed at evaluating long-term use of PPIs and its effects on female reproductive hormones as well as related clinical consequences. METHODS: A cross-sectional study was conducted in two outpatient gastroenterology clinics in the province of Khyber Pakhtunkhwa. This study included female patients who had been using PPIs on a regular basis for 3 months or more. RESULTS: In total of 101 participants, patients with sexual complaints have significantly altered levels of prolactin (p = 0.05), estrogen (p < 0.001) and progesterone (p = 0.001) than patient without sexual complaints. The frequency of amenorrhea (p < 0.001), cyclic disturbances (p < 0.001), breast augmentation (p = 0.001) and painful breast (p = 0.004) were statistically significant in patients with raised serum prolactin values. Serum values of Sex hormone binding globulin SHBG (p < 0.001), estradiol (p = 0.002) and total testosterone (p < 0.001) were significantly altered between normal prolactin and hyperprolactinemic patients. CONCLUSION: These findings suggest that long-term PPI use may cause endocrine hormone disturbances leading to sexual difficulties in women.

Auditing YouTube's recommendation system for ideologically congenial, extreme, and problematic recommendations.

Algorithms of social media platforms are often criticized for recommending ideologically congenial and radical content to their users. Despite these concerns, evidence on such filter bubbles and rabbit holes of radicalization is inconclusive. We conduct an audit of the platform using 100,000 sock puppets that allow us to systematically and at scale isolate the influence of the algorithm in recommendations. We test 1) whether recommended videos are congenial with regard to users' ideology, especially deeper in the watch trail and whether 2) recommendations deeper in the trail become progressively more extreme and come from problematic channels. We find that YouTube's algorithm recommends congenial content to its partisan users, although some moderate and cross-cutting exposure is possible and that congenial recommendations increase deeper in the trail for right-leaning users. We do not find meaningful increases in ideological extremity of recommendations deeper in the trail, yet we show that a growing proportion of recommendations comes from channels categorized as problematic (e.g., "IDW," "Alt-right," "Conspiracy," and "QAnon"), with this increase being most pronounced among the very-right users. Although the proportion of these problematic recommendations is low (max of 2.5%), they are still encountered by over 36.1% of users and up to 40% in the case of very-right users.

The influence of environment and Earnings on Prolonged existence and human fertility: A Deeper Dive into Asia's environmentally vulnerable nations.

This study inspects the impact of environmental deterioration and income on longevity and fertility in Asian countries, specifically the nations that are highly vulnerable to extreme weather. The study examines the data, covering two decades from 2000 to 2019. The empirical conclusions of the panel ARDL-PMG and the CS-ARDL econometric models indicate that environmental degradation leads to a decline in birth rate and life expectancy, while a rising income has a significant influence over longevity. However, increasing per capita income alone cannot solve the problem of population crisis in climatically susceptible countries. Therefore, the sample countries must prioritize climate action and formulate climate-resilient policies to add more years to the lives of their citizens. Similarly, for increasing childbirth the sample nations need to make peace with nature. The outcomes of this study are strong enough, as both the models support each other's findings, producing similar significant outcomes.

Promising impact of push-pull configuration into designed octacyclic naphthalene-based organic scaffolds for nonlinear optical amplitudes: a quantum chemical approach.

In opto-electronics, non-fullerene (NF) derivatives are regarded as efficient non-linear optical (NLO) materials. The present investigation was based on designing NF naphthalene-based derivatives (PCMD1-D9) with D-π-A configuration from PCMR. DFT analysis at M06/6-311G (d,p) level was accomplished to explore the photonic behavior of PCMD1-D9 compounds. Various kind of analysis like; UV-Vis, density of state (DOS), natural bond orbitals (NBOs), transition density matrix (TDM) and frontier molecular orbitals (FMOs) analyses were accomplished to understand the NLO properties of said chromophores. The configuration change led to considerable charge distribution over highest occupied and lowest unoccupied molecular orbitals with minimum band difference. The energy gap trend for all the entitled compounds was observed as; PCMD8 < PCMD5 = PCMD9 < PCMD6 < PCMD7 < PCMD4 < PCMD3 < PCMD2 < PCMD1 with the least band gap of 2.048 eV in PCMD8 among all the compounds. The UV-Visible spectrum of the entitled chromophores manifested high values of λmax in derivatives contrary to PCMR. Additionally, NBO findings explored effective intramolecular charge transfer and maximum energy of stabilization (34.31 kcal/mol) for PCMD8 chromophore. The highest linear polarizability (<α>) and dipole moment (µtot) values were exhibited by PCMD5 at 2.712 × 10-22. and 1.995 × 10-17 esu, respectively. PCMD8 push-pull configured molecular entity exhibited highest first hyper-polarizability (ßtot) at 4.747 × 10-27 esu and second hyper-polarizability at 6.867 × 10-32 esu. Overall, all the formulated chromophores exhibited significant NLO results contrary to PCMR. Hence, through this structural tailoring via various acceptors, effective NLO materials were obtained for optoelectronic applications.

Reactive oxygen species induced oxidative damage to DNA, lipids, and proteins of antibiotic-resistant bacteria by plant-based silver nanoparticles.

This study assesses the mechanism of action of plant-based silver nanoparticles (AgNPs) against antibiotic-resistant bacteria. We compared AgNPs synthesized through Salvia moorcroftiana and Origanum vulgare extracts and their conjugates with the antibiotic Ceftriaxone for their capacity to cause oxidative damage through reactive oxygen species (ROS). We quantified ROS in the cells of two bacterial strains after treating them with all AgNP types and observed that AgNPs were most effective in K. pneumoniae as they resulted in the highest ChS1 count (44,675), while in P. aeruginosa, Cfx-AgNPs induced the highest levels of ROS with ChS1 count of 56,865. DNA analysis showed that both plant-based AgNPs (O-AgNPs = 0.192 and S-AgNPs = 0.152) were most effective in K. pneumoniae and S-AgNPs (abs = 0.174) and O-Cfx-AgNPs (abs = 0.261) in P. aeruginosa. We observed a significant increase in the levels of conjugated dienes (86.4 µM) and malondialdehyde (172.25 nM) in the bacterial strains after treatment with AgNPs, compared to the control (71.65 µM and 18.064 nM, respectively, in K. pneumoniae and P. aeruginosa). These results indicate lipid peroxidation. AgNPs also increased the levels of protein thiols (0.672 nM) compared to the control (0.441 nM) in K. pneumoniae, except for Chem-AgNPs (0.21 nM). These results suggest that plant-based AgNPs are more effective in oxidizing bacterial DNA, protein, and lipids than Chem-AgNPs. Furthermore, protein oxidation varied between AgNPs alone and AgNPs-antibiotic conjugates. The highest levels of protein thiols were found in the samples treated with O-Cfx-AgNPs (0.672 nM and 0.525 nM in K. pneumoniae and P. aeruginosa, respectively). The results demonstrated that AgNPs kill bacteria by altering bacterial macromolecules such as DNA, lipids, and proteins.

Are the healthcare providers willing and able to respond to disasters: An assessment of tertiary health care system of Khyber Pakhtunkhwa.

For the tertiary health care system to provide adequate care during disasters, willing and able healthcare providers must be available to respond to the abnormal surge of the patients. Health care professionals (HCPs) constantly face a dilemma because of their profession to either respond to disasters or protect themselves. This study was conducted to assess the willingness and ability of HCPs working in the tertiary healthcare system of Khyber Pakhtunkhwa to respond to disasters. This cross-sectional survey was conducted in all the 8 tertiary care hospitals of the Khyber Pakhtunkhwa province of Pakistan. For different disaster scenarios, between 6% and 47% of HCP indicated their unwillingness, and between 3% & 41% of HCPs indicated that they were unable to respond to the given disaster scenarios. HCPs with childcare obligation indicated significantly lower willingness (p<0.05) to respond to earthquakes, MCIs, and an outbreak of Influenza, and SARS. Male HCPs showed a significantly (p<0.05) higher willingness to respond to earthquakes, MCIs, and an outbreak of Influenza as compared to their female counterparts. The overall ability indicated by HCPs for various disaster scenarios ranged between 54.1% [95% CI 0.503,0.578] for responding to victims of nuclear war and 96.4% [95% CI 0.947,0.976] for responding to conventional war. The HCPs who indicated childcare obligation showed a significantly lower ability (p<0.05) to respond to environmental disaster, influenza outbreak, and responding to victims of nuclear war. Female HCPs indicated significantly higher ability (p<0.05) as compared to their male counterparts. This survey provides an opportunity for the tertiary healthcare system to build on the findings and develop disaster mitigation plans to address the barriers to improving the HCPs' availability during disasters.

Facile Synthesis and DFT Analysis of Novel Thiazole-Based Hydrazones: An Experimental and Theoretical Perspective.

Hydrazone compounds with remarkable nonlinear optical (NLO) properties were found with vast applications due to their cost-effective synthesis and greater stability. Therefore, we synthesized hydrazone scaffolds (TCAH1-TCAH8) by condensation reaction, and their structural confirmation was accomplished with spectroscopic methods (1H-, 13C-NMR, and HRMS). Quantum chemical calculations were also performed at B3PW91/6-311G(d,p) functional of DFT to explore electronic, structural, and chemical properties. To understand the NLO responses of afore-said chromophores, various kinds of analyses such as natural bonding orbitals (NBOs), frontier molecular orbitals (FMOs), UV-vis analysis, and density of states (DOS) were performed. Findings showed that the HOMO-LUMO energy gap in TCAH8 (3.595 eV) was found to be lower than the TCAH1-TCAH7 (4.123-3.932 eV) with a large red shift which leads to a substantial NLO response. Furthermore, strong intramolecular interactions showed the highest stabilization energy (24.1 kcal mol-1) for TCAH8 in the NBO transitions, combined with the least binding energy. The significant NLO response of TCAH4 was explored with ⟨α⟩, ßtot, and ⟨γ⟩ values as 5.157 × 10-23, and 2.185 × 10-29, and 2.753 × 10-34 esu, respectively, among the entitled compounds. The recent findings may inspire scientists to develop extremely effective NLO materials for forthcoming hi-tech applications.

Synthesis of hydrazinylthiazole carboxylates: a mechanistic approach for treatment of diabetes and its complications.

Aim: The deaths of thousands of people and millions affected by diabetes mellitus triggered us to look for alternative possible solutions to cure diabetes and its complications. Materials & methods: A series of hydrazinylthiazole carboxylates (3a-n) was prepared by cyclocondensation reaction of thiosemicarbazones with ethyl 2-chloroacetoacetate. These compounds were screened for antidiabetic potential through α-amylase inhibition, antiglycation and antioxidant assays. Results & conclusion: Most of the compounds exhibited a promising antidiabetic property. Compounds 3e and 3h showed excellent α-amylase and glycation inhibition properties. The hemolytic assay indicated that all compounds are biocompatible. Docking studies carried out on α-amylase target showed correlation between in vitro inhibition and binding energy.

Quantum Chemical Exploration of A-π1-D1-π2-D2-Type Compounds for the Exploration of Chemical Reactivity, Optoelectronic, and Third-order Nonlinear Optical Properties.

Organic compounds exhibit significant nonlinear optical (NLO) properties and can be utilized in various areas like optical parameters, fiber optics, and optical communication. Herein, a series of chromophores (DBTD1-DBTD6) with an A-π1-D1-π2-D2 framework was derived from a prepared compound (DBTR) by varying the structure of π-spacer and terminal acceptor. The DBTR and its investigated compounds were optimized at the M06/6-311G(d,p) level of theory. Frontier molecular orbitals (FMOs), nonlinear optical (NLO) properties, global reactivity parameters (GRPs), natural bonding orbital (NBO), transition density matrix (TDM), molecular electrostatic potential (MEP), and natural population analysis (NPA) were accomplished at the abovementioned level to describe the NLO findings. DBTD6 has the lowermost band gap (2.131 eV) among all of the derived compounds. The decreasing order of highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap values was DBTR > DBTD1 > DBTD2 > DBTD3 > DBTD4 > DBTD5 > DBTD6. The NBO analysis was carried out to describe noncovalent interactions such as conjugative interactions and electron delocalization. From all of the examined substances, DBTD5 showed the highest λmax value at 593.425 nm (in the gaseous phase) and 630.578 nm (in chloroform solvent). Moreover, the ßtot and ⟨γ⟩ amplitudes of DBTD5 were noticed to be relatively greater at 1.140 × 10-27 and 1.331 × 10-32 esu, respectively. So, these outcomes disclosed that DBTD5 depicted the highest linear and nonlinear properties in comparison to the other designed compounds, which underlines that it could make a significant contribution to hi-tech NLO devices.

Sustainable remediation of dye-contaminated wastewater using novel cross-linked Hex-CCP-co-PPT microspheres.

The presence of dyes in contaminated water poses substantial dangers to the health of both humans and aquatic life. A process called precipitation polymerization was used to create unique cross-linked hexa-chlorocyclotriphosphazene-co-phenolphthalein (Hex-CCP-co-PPT) microspheres for the purpose of this research. Advanced methods such as X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential thermogravimetry (DTG) were used to characterise these microspheres. In a simulated solution, the performance of Hex-CCP-co-PPTs as a sorbent for removing MB dye was investigated, and the results showed an unprecedentedly high removal rate of 88.4% for MB. Temperature of 25 °C, a Hex-CCP-co-PPTs dose of 40 mg, an MB concentration of 20 ppm, an MB solution volume of 20 mL, a contact time of 40 min, and a pH of 9 were found to be the optimal experimental conditions. According to the results of the kinetic and adsorption analyses, the PSO and Langmuir adsorption models are the best ones to use. These models favour the chemi-sorption nature and mono-layered adsorption of MB in comparison to Hex-CCP-co-PPTs. Importantly, the thermodynamic analysis demonstrated that the process of removing MB by utilizing Hex-CCP-co-PPTs was endothermic and occurred spontaneously. These findings highlight the potential application of Hex-CCP-co-PPT microspheres in Algal Membrane Bioreactors (AMBRs) for the efficient and sustainable removal of dye from wastewater. This would contribute to the protection of ecosystems as well as the public's health.

Use of remote sensing-based pressure-state-response framework for the spatial ecosystem health assessment in Langfang, China.

Land use/land cover changes are occurring at an unprecedented rate and scale because of the economic development that has jeopardized the ecosystem's health. Ecosystem health should be studied and monitored at spatiotemporal scale to promote sustainable development and ecological civilization. The goal of this study was to assess the spatial ecosystem health of Langfang at the city and administrative levels using city's regional characteristics. Remote sensing-based pressure-state-response (PSR) framework, analytical hierarchy process (AHP), and principal component analysis (PCA) were utilized for spatial ecosystem health index (SEHI) formulation, indicator weighting, and indicator selection in several epochs (1990, 2003, 2013, and 2021), respectively. SEHI was formulated by combining subindices of pressure, state and response. The spatial ecosystem pressure index (SEIP) identified that the pressure was increasing on the ecosystem. In contrast, the spatial ecosystem state index (SEIS) pointed out an improvement in the state of the ecosystem since 1990. The worst state of the ecosystem was observed for the year 2013. The spatial ecosystem response index (SEIR) indicated that the response of the ecosystem towards the exerted pressures and states remained variable; however, it was reasonably good in 1990. All the administrative units of Langfang were associated with a healthy score for the spatial ecosystem health index (SEHI) for 1990 (pre-industrialization epoch), while the SEHI significantly reduced in 2013 (industrialization epoch) however improved for the later epochs (circular economy and ecological civilization epoch). The SEHI was moderately healthy for Dachang, Dacheng, Guan, Guangyang, and Yongqing while relatively healthy for the remaining administrative units in 2021. SEHI identified that spatial health has been improving since 2003 though not reaching the 1990's level for Langfang. Therefore, efforts should be focused on minimizing pressure and stabilizing the state to improve the spatial ecosystem health of Langfang. The developed SEHI can assist policymakers in analyzing regional health, identifying development strategies, driving environmental restoration, and quantifying needed changes.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

The Corey-Seebach Reagent in the 21st Century: A Review.

The Corey-Seebach reagent plays an important role in organic synthesis because of its broad synthetic applications. The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol under acidic conditions, followed by deprotonation with n-butyllithium. A large variety of natural products (alkaloids, terpenoids, and polyketides) can be accessed successfully by utilizing this reagent. This review article focuses on the recent contributions (post-2006) of the Corey-Seebach reagent towards the total synthesis of natural products such as alkaloids (lycoplanine A, diterpenoid alkaloids, etc.), terpenoids (bisnorditerpene, totarol, etc.), polyketide (ambruticin J, biakamides, etc.), and heterocycles such as rodocaine and substituted pyridines, as well and their applications towards important organic synthesis.

Interference mitigation in intentional jammers aided non-uniform heterogeneous cellular networks.

Coverage and capacity are optimized in fifth generation (5G) networks by small base station (SBS) distribution in the coverage realm of macro base station (MBS). However, system performance is significantly reduced by inter-cell interference (ICI) because of the orthogonal frequency division multiple access assumption. In addition to ICI, this work considers intentional jammers' interference (IJI) due to the presence of jammers. These Jammers try to inject undesirable energies into the legitimate communication band, which significantly degrade uplink (UL) signal-to-interference ratio (SIR). To reduce ICI and IJI, in this work, we employ SBS muting, where the SBSs near MBS are switched off. To further mitigate ICI and IJI, we use one of the effective interference management schemes a.k.a reverse frequency allocation (RFA). We presume that due to mitigation in ICI and IJI, the UL coverage performance of the proposed network model can be further improved.

4-Adamantyl-(2-(arylidene)hydrazinyl)thiazoles as potential antidiabetic agents: experimental and docking studies.

Aim: To develop an efficient and cost-effective antidiabetic agent. Methods: A simple and convenient Hantzsch synthetic strategy was used to prepare 4-adamantyl-(2-(arylidene)hydrazinyl)thiazoles. Results: Fifteen newly established structures of 4-adamantyl-(2-(arylidene)hydrazinyl)thiazoles were tested for their α-amylase, antiglycation and antioxidant activities. Almost all tested compounds showed excellent α-amylase inhibition. Compounds 3a and 3j exhibited the highest potency, with IC50 values of 16.34 ± 2.67 and 16.64 ± 1.12 µM, respectively. Compounds 3c and 3i exhibited comparable antiglycation potential with the standard, aminoguanidine. The antioxidant potential of compound 3g was found to be excellent, with an IC50 value of 28.19 ± 0.2563 µM. The binding interactions of compound 3a (binding energy = -8.833 kcal/mol) with human pancreatic α-amylase identified 3a as a potent α-amylase inhibitor. Conclusion: Enrichment of established structures with more electron-donating functionalities may assist/lead to the development of more potent antidiabetic drugs.

Diabetes is one of the major causes of death in the present era. To combat damaging processes associated with diabetes, called glycation and oxidation, we prepared a series of compounds called 4-adamantyl-(2-(arylidene)hydrazinyl)thiazoles. The established structures were tested for their antidiabetic potential. The compounds 4-adamantyl-(2-(4-chlorobenzylidene)hydrazinyl)thiazole and 4-adamantyl-(2-(2-chlorobenzylidene)hydrazinyl)thiazole showed the highest potency. The compounds 4-adamantyl-(2-(4-bromobenzylidene)hydrazinyl)thiazole and 4-adamantyl-(2-(2-hydroxybenzylidene)hydrazinyl)thiazole exhibited comparable antiglycation potential. The antioxidant potential of compound 4-adamantyl-(2-(3-nitrobenzylidene)hydrazinyl)thiazole was found to be excellent. A further test was used to check toxicity and all compounds were found to be biocompatible. We also investigated, through docking studies, the way in which these compounds interact with the human proteins albumin and pancreatic α-amylase.

Synthesis of Fluorinated Hydrazinylthiazole Derivatives: A Virtual and Experimental Approach to Diabetes Management.

A novel series of fluorophenyl-based thiazoles was synthesized following the Hanztsch method. All of the compounds were initially verified with physical parameters (color, melting point, retardation factor (R f)), which were further confirmed by several spectroscopic methods, including ultraviolet-visible (UV-visible), Fourier-transform infrared (FTIR), 1H, 13C, 19F NMR, and high-resolution mass spectrometry (HRMS). The binding interactions of all compounds were studied using a molecular docking simulation approach. Furthermore, each compound was evaluated for its alpha(α)-amylase, antiglycation, and antioxidant potentials. The biocompatibility of all compounds was checked with an in vitro hemolytic assay. All synthesized scaffolds were found biocompatible with minimal lysis of human erythrocytes as compared to the standard Triton X-100. Among the tested compounds, the analogue 3h (IC50 = 5.14 ± 0.03 µM) was found to be a highly potent candidate against α-amylase as compared to the standard (acarbose, IC50 = 5.55 ± 0.06 µM). The compounds 3d, 3f, 3i, and 3k exhibited excellent antiglycation inhibition potential with their IC50 values far less than the standard amino guanidine (IC50 = 0.403 ± 0.001 mg/mL). The antidiabetic potential was further supported by docking studies. Docking studies revealed that all synthesized compounds exhibited various interactions along enzyme active sites (pi-pi, H-bonding, van der Waals) with varied binding energies.