Recent development and strategies towards target interactions: Synthesis, characterization and in silico analysis of benzimidazole based thiadiazole as potential anti-Alzheimer agents.

In the current research study, we aim to design and synthesize highly potent hybrid analogs of benzimidazole derived thiadiazole based Schiff base derivatives which can combat the cholinesterase enzymes (acetylcholinesterase and butyrylcholinesterase) accountable for developing Alzheimer's disease. In this context, we have synthesized 15 analogs of benzimidazole based thiadiazole derivatives, which were subsequently confirmed through spectroscopic techniques including 1H NMR, 13C NMR and HREI-MS. Biological investigation of all the analogs revealed their varied acetylcholinesterase inhibitory potency covering a range between 3.20 ± 0.10 µM to 20.50 ± 0.20 µM as well as butyrylcholinesterase inhibitory potential with a range of 4.30 ± 0.50 µM to 20.70 ± 0.50 µM when compared with the standard drug Donepezil having IC50 = 6.70 ± 0.20 µM for AChE and 7.90 ± 0.10 µM for BuChE. The promising inhibition by the analogs was evaluated in SAR analysis, where analog-1 (IC50 = 3.20 ± 0.10 µM for AChE and 4.30 ± 0.50 µM for BuChE), analog-4 (IC50 = 4.30 ± 0.30 µM for AChE and 5.50 ± 0.20 µM for BuChE) and analog-5 (IC50 = 4.10 ± 0.30 µM for AChE and 4.60 ± 0.40 µM for BuChE) were found as the lead candidates. Moreover, molecular docking and ADME analysis were conducted to explore the better binding interactions and drugs likeness respectively.

Design, Synthesis, In Vitro Biological Evaluation and In Silico Molecular Docking Study of Benzimidazole-Based Oxazole Analogues: A Promising Acetylcholinesterase and Butyrylcholinesterase Inhibitors.

Alzheimer's disease (AD) is a degenerative neurological condition that severely affects the elderly and is clinically recognised by a decrease in cognition and memory. The treatment of this disease has drawn considerable attention and sparked increased interest among the researchers in this field as a result of a number of factors, including an increase in the population of patients over time, a significant decline in patient quality of life, and the high cost of treatment and care. The current work was carried out for the synthesis of benzimidazole-oxazole hybrid derivatives as efficient Alzheimer's inhibitors and as a springboard for investigating novel anti-chemical Alzheimer's prototypes. The inhibition profiles of each synthesised analogue against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were assessed. All the synthesized benzimidazole-based oxazole analogues displayed a diverse spectrum of inhibitory potentials against targeted AChE and BuChE enzymes when compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 M and 4.50 ± 0.11 µM, respectively). The most active AChE and BuChE analogues were discovered to be analogues 9 and 14, with IC50 values of 0.10 ± 0.050 and 0.20 ± 0.050 µM (against AChE) and 0.20 ± 0.050 and 0.30 ± 0.050 µM (against BuChE), respectively. The nature, number, position, and electron-donating and -withdrawing effects on the phenyl ring were taken into consideration when analysing the structure-activity relationship (SAR). Molecular docking studies were also carried out on the active analogues to find out how amino acids bind to the active sites of the AChE and BuChE enzymes that were being studied.

Synthesis, DFT Studies, Molecular Docking and Biological Activity Evaluation of Thiazole-Sulfonamide Derivatives as Potent Alzheimer's Inhibitors.

Alzheimer's disease is a major public brain condition that has resulted in many deaths, as revealed by the World Health Organization (WHO). Conventional Alzheimer's treatments such as chemotherapy, surgery, and radiotherapy are not very effective and are usually associated with several adverse effects. Therefore, it is necessary to find a new therapeutic approach that completely treats Alzheimer's disease without many side effects. In this research project, we report the synthesis and biological activities of some new thiazole-bearing sulfonamide analogs (1-21) as potent anti-Alzheimer's agents. Suitable characterization techniques were employed, and the density functional theory (DFT) computational approach, as well as in-silico molecular modeling, has been employed to assess the electronic properties and anti-Alzheimer's potency of the analogs. All analogs exhibited a varied degree of inhibitory potential, but analog 1 was found to have excellent potency (IC50 = 0.10 ± 0.05 µM for AChE) and (IC50 = 0.20 ± 0.050 µM for BuChE) as compared to the reference drug donepezil (IC50 = 2.16 ± 0.12 µM and 4.5 ± 0.11 µM). The structure-activity relationship was established, and it mainly depends upon the nature, position, number, and electron-donating/-withdrawing effects of the substituent/s on the phenyl rings.

Synthetic transformation of 6-Fluoroimidazo[1,2-a]Pyridine-3-carbaldehyde into 6-Fluoroimidazo[1,2-a]Pyridine-Oxazole Derivatives: In vitro urease inhibition and in silico study.

Purpose: Ulcer is a serious disease that is caused due to different bacteria and over usage of various NSAIDs which caused to reduce the defensive system of stomach. Therefore, some novel series are needed to overcome these issues. Methods: Oxazole-based imidazopyridine scaffolds (4a-p) were designed and synthesized by two step reaction protocol and then subjected to urease inhibition profile (in vitro). All the newly afforded analogs (4a-p) were found potent and demonstrated moderate to significant inhibition profile. Results: Particularly, the analogs 4i (IC50 = 5.68 ± 1.66 µM), 4o (IC50 = 7.11 ± 1.24 µM), 4 g (IC50 = 9.41 ± 1.19 µM) and 4 h (IC50 = 10.45 ± 2.57 µM) were identified to be more potent than standard thiourea drug (IC50 = 21.37 ± 1.76 µM). Additionally, the variety of spectroscopic tools such as 1H NMR, 13C NMR and HREI-MS analysis were employed to confirm the precise structures of all the newly afforded analogs. Discussion: The structure-activity relationship (SAR) studies showed that analogs possess the substitution either capable of furnishing strong HB like -OH or had strong EW nature such as -CF3 & -NO2 groups displayed superior inhibitory potentials than the standard thiourea drug. A good PLI (protein-ligand interaction) profile was shown by most active analogs when subjected to molecular study against corresponding target with key significant interactions such as pi-pi stacking, pi-pi T shaped and hydrogen bonding.

Investigation of novel bis-thiadiazole bearing schiff base derivatives as effective inhibitors of thymidine phosphorylase: Synthesis, in vitro bioactivity and molecular docking study.

Thymidine phosphorylase (TP) is an angiogenic enzyme. It is crucial for the development, invasion and metastasis of tumors as well as angiogenesis. In our current research, we examine how structurally changing bis-thiadiazole bearing bis-schiff bases affects their ability to inhibit TP. Through the oxidative cyclization of pyridine-based bis-thiosemicarbazone with iodine, a series of fourteen analogs of bis-thiadiazole-based bis-imines with pyridine moiety were developed. Newly synthesized scaffolds were assessed in vitro for their thymidine phosphorylase inhibitory potential and showed moderate to good inhibition profile. Eleven scaffolds such as 4a-4d,4f-4 h and 4j-4 m were discovered to be more effective than standard drug at inhibiting the thymidine phosphorylase enzyme with IC50 values of 1.16 ± 1.20, 1.77 ± 1.10, 2.48 ± 1.30, 12.54 ± 1.60, 14.63 ± 1.70, 15.53 ± 1.80, 17.47 ± 1.70, 18.98 ± 1.70, 19.53 ± 1.50, 22.73 ± 2.40 and 24.87 ± 2.80 respectively, while remaining three analogs such as 4n, 4i and 4ewere found to be more potent, but they were less potent than the standard drug. All analogs underwent SAR studies based on the pattern of substitutions around the aryl part of the bis-thiadiazole skeleton. The most active analogs in the synthesized series were then molecular docking study performed to investigate their interactions of active part of enzyme. The results showed that remarkable interactions were exhibited by these analogs with the targeted enzymes active sites. Furthermore, to confirm the structure of synthesized analogs by employing spectroscopic tools such as HREI-MS and NMR.

Green synthesis of SrO bridged LaFeO3/g-C3N4 nanocomposites for CO2 conversion and bisphenol A degradation with new insights into mechanism.

Very recently the green synthesis routes of nanomaterials have attracted massive attention as it overcome the sustainability concerns of conventional synthesis approaches. With this heed, in this novel research work we have synthesized the g-C3N4 nanosheets based nanocomposites by utilizing Eriobotrya japonica as mediator and stabilizer agent. Our designed bio-caped and green g-C3N4 nanosheets based nanocomposites have abundant organic functional groups, activated surface and strong adsorption capability which are very favorable for conversion CO2 into useful products and bisphenol A degradation. Beneficial to further upgrade the performances of g-C3N4 nanosheets, the resulting pristine g-C3N4 nanosheets are coupled with LaFeO3 nanosheets via SrO bridge. Based on our experimental results such as TEM, XRD, DRS, TPD, TGA, PL, PEC and FS spectra linked with OH amount it is confirmed that the biologically mediated green g-C3N4 nanosheets are eco-friendly, highly efficient and stable. Furthermore, the coupling of LaFeO3 nanosheets enlarged the surface area, enhanced the charge separation, while the insertion of SrO bridge worked as facilitator for electron transportation and photo-electron modulation. In contrast to pristine green g-C3N4 nanosheets (GCN), the activities of final resulting sample 6LFOS-(4SrO)-GCN are improved by 8.0 times for CO2 conversion (CH4 = 4.2, CO = 9.2 µmol g-1 h-1) and 2.5-fold for bisphenol A degradation (88%) respectively. More specifically, our current research work will open a new gateway to design cost effective, eco-friendly and biological inspired green nanomaterials for CO2 conversion and organic pollutants degradation which will further support the net zero carbon emission manifesto and the optimization of carbon neutrality level.

Synthesis and Molecular Docking of New Bis-Thiazolidinone-Based Chalcone Analogs as Effective Inhibitors of Acetylcholinesterase and Butyrylcholinesterase.

This work reports the convenient strategy for the synthesis of bis-thiazolidinone based chalcone analogs (1-20) from readily available thiosemicarbazide hydrochloride, ammonium thiocyanate and benzaldehyde. All the newly afforded bis-thiazolidinone based chalcone analogs (1-20) were screened in vitro for their acetylcholinesterase and butyrylcholinesterase inhibition profile. It was noteworthy, that all the synthetic analogs (except analogs 10, 12 and 14, which are found to be inactive) showed moderate to good inhibitory potentials on screening against acetylcholinesterase having range of inhibitory with IC50 values from 0.070±0.050 to 7.60±0.10 µM, and similarly for butyrylcholinesterase with range IC50 values from 0.10±0.050 µM to 10.70±0.20 µM, respectively as compared to standard Donepezil inhibitor (IC50 =2.16±0.12 µM), (IC50 =4.5±0.11 µM).Among the series, the analogs with hydroxy group showed superior inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes. Therefore, analog 20 (IC50 =0.070±0.050 µM), (IC50 =0.10±0.050 µM) bearing trihydroxy substitutions on ortho-, meta- and para-position of both rings A and B was found to be the most active inhibitor of acetylcholinesterase and butyrylcholinesterase enzymes among the current synthesized series (1-23). Analog 19 (IC50 =0.15±0.050 µM), (IC50 =0.20±0.050 µM) bearing dihydroxy substitutions on ortho- and meta-position of both ring A and ring B was identified as the second most potent inhibitor against both these enzymes. Interestingly, the compound (16) (IC50 =1.50±0.10 µM against AChE) has a better selectivity index (2.60) than standard Donepezil drug (2.083) for AChE over BuChE. The different types of spectroscopic techniques such as HR-EI-MS, 1 H- and 13 C- NMR were used to confirm the structure of all the newly synthetics analogs. To find structure-activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data.

Investigating the gender differences in indoor thermal comfort perception for summer and winter seasons and comparison of comfort temperature prediction methods.

Formulation of indoor thermal comfort guidelines is challenging task considering the fact that these guidelines are supposed to address both, the expectations of the building occupants' regarding indoor thermal comfort, and optimize building energy use, under aggravating conditions of outdoor climate and availability and price volatility of energy. Therefore, a field survey was conducted to assess indoor thermal comfort in two female and three male dormitory buildings. Afterwards, a comparative analysis of three comfort temperature prediction models (linear, cubic and logistic) was conducted. In total, 971 survey forms were collected during the two seasons (summer and winter). Two-third of the data was used to develop the models, while remaining one-third was used to test the accuracies. Although thermal sensation votes of both genders were statistically different, no statistical difference in indoor comfort temperature between the two genders was observed. Comfort temperatures were calculated as 26.4 °C and 27.8 °C during summer and 22.7 °C and 22.4 °C during winters for female and male occupants respectively, using liner regression method. Following the Griffth's method mean operative comfort temperatures were calculated as 26.8 ± 1.5 °C and 27.6 ± 1.7 °C during summer and 22.7 ± 2.3 °C and 22.3 ± 2.0 °C during winter for female and male occupants respectively. Percentage accuracies of three prediction methods under study showed better performance of logistic regression.

Multipotent Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease: Synthesis, Biological Analysis and Molecular Docking Study of Benzimidazole-Based Thiazole Derivatives.

Twenty-four analogues of benzimidazole-based thiazoles (1-24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.

New Biologically Hybrid Pharmacophore Thiazolidinone-Based Indole Derivatives: Synthesis, In Vitro Αlpha-Amylase and Αlpha-Glucosidase Along with Molecular Docking Investigations.

Amylase and glucosidase enzymes are the primary harmful source in the development of the chronic condition known as diabetes mellitus. The main function of these enzymes is to break the macromolecules into simple sugar units which are directly involved in the solubility of blood, hence increasing blood glucose levels. To overcome this effect, there is a need for a potent and effective inhibitor that inhibits the conversion of macromolecules of sugar into its smaller units. In this regard, we synthesized thiazolidinone-based indole derivatives (1−20). The synthesized derivatives were evaluated for α-amylase and α-glucosidase inhibitory activity. Different substituted derivatives were found with moderate to good potentials having IC50 values ranging, for α-amylase, from 1.50 ± 0.05 to 29.60 ± 0.40 µM and, for α-glucosidase, from IC50 = 2.40 ± 0.10 to 31.50 ± 0.50 µM. Among the varied substituted compounds, the most active analogs four (1.80 ± 0.70 and 2.70 ± 0.70), five (1.50 ± 0.05 and 2.40 ± 0.10, respectively) of the series showed few folds better inhibitory activity than standard drug acarbose (IC50 = 10.20 ± 0.10 and 11.70 ± 0.10 µM, respectively). Moreover, structure−activity relationship (SAR) was established and binding interactions were analyzed for ligands and proteins (α-amylase and α-glucosidase) through a molecular docking study.

Synthesis, In Vitro Biological Evaluation and In Silico Molecular Docking Studies of Indole Based Thiadiazole Derivatives as Dual Inhibitor of Acetylcholinesterase and Butyrylchloinesterase.

The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (1-16) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue 8 was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including 1H, 13CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure-activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.

Synthesis, In Vitro Anti-Microbial Analysis and Molecular Docking Study of Aliphatic Hydrazide-Based Benzene Sulphonamide Derivatives as Potent Inhibitors of α-Glucosidase and Urease.

A unique series of sulphonamide derivatives was attempted to be synthesized in this study using a new and effective method. All of the synthesized compounds were verified using several spectroscopic methods, including FTIR, 1H-NMR, 13C-NMR, and HREI-MS, and their binding interactions were studied using molecular docking. The enzymes urease and α-glucosidase were evaluated against each derivative (1-15). When compared to their respective standard drug such as acarbose and thiourea, almost all compounds were shown to have excellent activity. Among the screened series, analogs 5 (IC50 = 3.20 ± 0.40 and 2.10 ± 0.10 µM) and 6 (IC50 = 2.50 ± 0.40 and 5.30 ± 0.20 µM), emerged as potent molecules when compared to the standard drugs acarbose (IC50 = 8.24 ± 0.08 µM) and urease (IC50 = 7.80 ± 0.30). Moreover, an anti-microbial study also demonstrated that analogs 5 and 6 were found with minimum inhibitory concentrations (MICs) in the presence of standard drugs streptomycin and terinafine.

Synthesis of Novel Benzimidazole-Based Thiazole Derivatives as Multipotent Inhibitors of α-Amylase and α-Glucosidase: In Vitro Evaluation along with Molecular Docking Study.

In this study, hybrid analogs of benzimidazole containing a thiazole moiety (1-17) were afforded and then tested for their ability to inhibit α-amylase and α-glucosidase when compared to acarbose as a standard drug. The recently available analogs showed a wide variety of inhibitory potentials that ranged between 1.31 ± 0.05 and 38.60 ± 0.70 µM (against α-amylase) and between 2.71 ± 0.10 and 42.31 ± 0.70 µM (against α-glucosidase) under the positive control of acarbose (IC50 = 10.30 ± 0.20 µM against α-amylase) (IC50 = 9.80 ± 0.20 µM against α-glucosidase). A structure-activity relationship (SAR) study was carried out for all analogs based on substitution patterns around both rings B and C respectively. It was concluded from the SAR study that analogs bearing either substituent(s) of smaller size (-F and Cl) or substituent(s) capable of forming hydrogen bonding (-OH) with the catalytic residues of targeted enzymes enhanced the inhibitory potentials. Therefore, analogs 2 (bearing meta-fluoro substitution), 3 (having para-fluoro substitution) and 4 (with ortho-fluoro group) showed enhanced potency when evaluated against standard acarbose drug with IC50 values of 4.10 ± 0.10, 1.30 ± 0.05 and 1.90 ± 0.10 (against α-amylase) and 5.60 ± 0.10, 2.70 ± 0.10 and 2.90 ± 0.10 µM (against α-glucosidase), correspondingly. On the other hand, analogs bearing substituent(s) of either a bulky nature (-Br) or that are incapable of forming hydrogen bonds (-CH3) were found to lower the inhibitory potentials. In order to investigate the binding sites for synthetic analogs and how they interact with the active areas of both targeted enzymes, molecular docking studies were also conducted on the potent analogs. The results showed that these analogs adopted many important interactions with the active areas of enzymes. The precise structure of the newly synthesized compounds was confirmed using several spectroscopic techniques as NMR and HREI-MS.

New Triazinoindole Bearing Benzimidazole/Benzoxazole Hybrids Analogs as Potent Inhibitors of Urease: Synthesis, In Vitro Analysis and Molecular Docking Studies.

Twenty-four analogs based on triazinoindole bearing benzimidazole/benzoxazole moieties (1-25) were synthesized. Utilizing a variety of spectroscopic methods, including 1H-, 13C-NMR, and HREI-MS, the newly afforded compounds (1-25) were analyzed. The synthesized analogs were tested against urease enzyme (in vitro) as compared to the standard thiourea drug. All triazinoindole-based benzimidazole/benzoxazole analogs (1-25) exhibited moderate to excellent inhibition profiles, having IC50 values of 0.20 ± 0.01 to 36.20 ± 0.70 µM when evaluated under the positive control of thiourea as a standard drug. To better understand the structure-activity relationship, the synthesized compounds were split into two groups, "A" and "B." Among category "A" analogs, analogs 8 (bearing tri-hydroxy substitutions at the 2,4,6-position of aryl ring C) and 5 (bearing di-hydroxy substitutions at the 3,4-position of aryl ring C) emerged as the most potent inhibitors of urease enzyme and displayed many times more potency than a standard thiourea drug. Besides that, analog 22 (which holds di-hydroxy substitutions at the 2,3-position of the aryl ring) and analog 23 (bearing ortho-fluoro substitution) showed ten-fold-enhanced inhibitory potential compared to standard thiourea among category "B" analogs. Molecular docking studies on the active analogs of each category were performed; the results obtained revealed that the presence of hydroxy and fluoro-substitutions on different positions of aryl ring C play a pivotal role in binding interactions with the active site of the targeted urease enzyme.

Synthesis of New Triazole-Based Thiosemicarbazone Derivatives as Anti-Alzheimer's Disease Candidates: Evidence-Based In Vitro Study.

Triazole-based thiosemicarbazone derivatives (6a-u) were synthesized then characterized by spectroscopic techniques, such as 1HNMR and 13CNMR and HRMS (ESI). Newly synthesized derivatives were screened in vitro for inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All derivatives (except 6c and 6d, which were found to be completely inactive) demonstrated moderate to good inhibitory effects ranging from 0.10 ± 0.050 to 12.20 ± 0.30 µM (for AChE) and 0.20 ± 0.10 to 14.10 ± 0.40 µM (for BuChE). The analogue 6i (IC50 = 0.10 ± 0.050 for AChE and IC50 = 0.20 ± 0.050 µM for BuChE), which had di-substitutions (2-nitro, 3-hydroxy groups) at ring B and tri-substitutions (2-nitro, 4,5-dichloro groups) at ring C, and analogue 6b (IC50 = 0.20 ± 0.10 µM for AChE and IC50 = 0.30 ± 0.10 µM for BuChE), which had di-Cl at 4,5, -NO2 groups at 2-position of phenyl ring B and hydroxy group at ortho-position of phenyl ring C, emerged as the most potent inhibitors of both targeted enzymes (AChE and BuChE) among the current series. A structure-activity relationship (SAR) was developed based on nature, position, number, electron donating/withdrawing effects of substitution/s on phenyl rings. Molecular docking studies were used to describe binding interactions of the most active inhibitors with active sites of AChE and BuChE.

Benzimidazole Bearing Thiosemicarbazone Derivatives Act as Potent α-Amylase and α-Glucosidase Inhibitors; Synthesis, Bioactivity Screening and Molecular Docking Study.

Diabetes mellitus is one of the most chronic metabolic diseases. In the past few years, our research group has synthesized and evaluated libraries of heterocyclic analogs against α-glucosidase and α-amylase enzymes and found encouraging results. The current study comprises the evaluation of benzimidazole-bearing thiosemicarbazone as antidiabetic agents. A library of fifteen derivatives (7-21) was synthesized, characterized via different spectroscopic techniques such as HREI-MS, NMR, and screened against α-glucosidase and α-amylase enzymes. All derivatives exhibited excellent to good biological inhibitory potentials. Derivatives 19 (IC50 = 1.30 ± 0.20 µM and 1.20 ± 0.20 µM) and 20 (IC50 = 1.60 ± 0.20 µM and 1.10 ± 0.01 µM) were found to be the most potent among the series when compared with standard drug acarbose (IC50 = 11.29 ± 0.07 and 11.12 ± 0.15 µM, respectively). These derivatives may potentially serve as the lead candidates for the development of new therapeutic representatives. The structure-activity relationship was carried out for all molecules which are mainly based upon the pattern of substituent/s on phenyl rings. Moreover, in silico docking studies were carried out to investigate the active binding mode of selected derivatives with the target enzymes.

FORMULATION DEVELOPMENT OF TOPICAL CREAM LOADED WITH ANANAS COMOSUS EXTRACT: IN VIVO EVALUATION FOR CHANGES IN SKIN BARRIER FUNCTION USING BIOPHYSICAL TECHNIQUES.

The prime objective of current investigation was to develop a topical skin care cream (w/o) loaded with Ananas comosus extract versus placebo control, and evaluated non-invasively for changes in skin barrier function i.e., epidermal hydration levels and transepidermal water loss (TEWL), on healthy human volunteers. Active cream carrying 2% extract of Ananas comosus in the internal phase of w/o emulsion was prepared while placebo contained no extract. Stability assessment of both creams was performed at various storage conditions 8, 25, 40 degrees C, 40 degrees C + 75% RH (relative humidity) and 50 degrees C. Effects on epidermal hydration and TEWL were observed by applying active cream at one side and placebo on the other side of face by 11 healthy human volunteers during 12 weeks period using Corneometer MPA5 and Tewameter MPA5. Results indicated that both creams (active and placebo) remained stable at all storage conditions. All samples manifested non-Newtonian, shear thinning behavior with increasing shear rate, whereas statistical interpretation indicated that effects of active cream were superior than placebo, as it significantly (p = 0.05) improves the epidermal hydration levels up to 56.74% and reduces TEWL up to -73.19% at the end of study period compared to baseline value. The surface evaluation of living skin (SELS) parameters SEr, SEsc, SEsm, SEw were also assessed and indicated a significant (p = 0.05) reduction. Conclusively, creams loaded with Ananas comosus extract exhibit better physicochemical stability and represent a propitious improvement in skin barrier function, used as a functional moisturizing and anti-aging ingredient in topical skincare products.

IN VIVO EVALUATION OF SKIN IRRITATION POTENTIAL, MELASMA AND SEBUM CONTENT FOLLOWING LONG TERM APPLICATION OF SKIN CARE CREAM IN HEALTHY ADULTS, USING NON-INVASIVE BIOMETROLOGICAL TECHNIQUES.

The present investigation was conducted to evaluate non-invasively, various functional skin parameters i.e., irritation potential, melasma and sebum contents following long term application of topical cream (w/o) loaded with 2% methanolic extract of Ananas comosus L. versus placebo control (base) in healthy adults. Healthy human volunteers (n = 11, aged 20-30 years) were recruited for investigation and written informed consent was taken from each volunteer. In this single blinded study every volunteer applied formulation on one side of face and placebo on the other side of face twice daily for a period of 12 weeks (three months). Different skin parameters i.e., skin irritancy, melasma, and sebum contents were measured on both sides of face at baseline and after two weeks interval, using photometric device Mexameter and Sebumeter in a draught free room with modulated conditions of temperature (22-25°C) and humidity (55-60%). It was evident from the results that no primary skin irritancy was observed with patch test. Besides, statistical interpretation indicates that treatment with formulation is superior to placebo because it significantly (p ≤ 0.05) reduced the skin irritancy, melasma and sebum secretions throughout the study and reaching maximum -20.76 ± 0.89, -54.2 ± 0.37 and -40.71 ± 0.75%, respectively, at the end of study period. Antioxidant activity of extract was 92% compared to standard antioxidant. Conclusively, active cream loaded with fruit extract was well tolerated by all the volunteers and suitable to treat contact dermatitis, greasy skin, acne and seborrheic dermatitis and augmenting beauty and attraction by depigmentation of human skin. So, in the future, there is need to clinically evaluate these formulations in patients with compromised skin functions i.e., contact dermatitis, melasma, and acne vulgaris in order to explore the actual potential of this fruit.

Impact of behavioral biases on investment decisions and the moderation effect of financial literacy; an evidence of Pakistan.

Th is study offers empirical insights into investor behavior and its correlation with various behavioral biases in the context of investment decisions in the Pakistan Stock Exchange (PSX). Data was collected through a structured questionnaire from 261 individual investors in Pakistan. The study employs hierarchical regression analysis to test the hypothesis. It considers several behavioral biases, and statistically, anchoring and adjustment, overconfidence, and herding show a significant impact. The study uses financial literacy to examine its moderating effects on these biases, and the result suggests that it significantly influences behavioral biases related to investment decisions. The results underscore the unique investment behaviors in emerging markets, contrasting with established norms in well-developed financial markets. These findings can inform policymakers and stock market authorities about investor decision-making in emerging economies.

In silico molecular modeling and in vitro biological screening of novel benzimidazole-based piperazine derivatives as potential acetylcholinesterase and butyrylcholinesterase inhibitors.

New series of benzimidazole incorporating piperazine moieties in single molecular framework has been reported. The structures of the synthesized derivatives were assigned by 1H-NMR, 13C-NMR, and HR-MS techniques. The hybrid derivatives were evaluated for their acetylcholinesterase and butyrylcholinesterase inhibition effect. All the synthesized analogs showed good to moderate inhibitory effect ranging from IC50 value 0.20 ± 0.01 µM to 0.50 ± 0.10 µM for acetylcholinesterase and from IC50 value 0.25 ± 0.01 µM to 0.70 ± 0.10 µM for butyrylcholinesterase except one that showed least potency with IC50 value 1.05 ± 0.1 µM and 1.20 ± 0.1 µM. The differences in inhibitory potential of synthesized compounds were due to the nature and position of substitution attached to the main ring. Additionally, molecular docking study was carried out for most active in order to explore the binding interactions established by ligand (active compounds) with the active residues of targeted AChE & BuChE enzyme.