BMC Chemistry最新文献

In order to explore the role of topological indices for predicting physio-chemical properties of anti-HIV drugs, this research uses python program-based algorithms to compute topological indices as well as machine learning algorithms. Degree-based topological indices are calculated using Python algorithm, providing important information about the structural behavior of drugs that are essential to their anti-HIV effectiveness. Furthermore, machine learning algorithms analyze the physio-chemical properties that correspond to anti-HIV activities, making use of their ability to identify complex trends in large, convoluted datasets. In addition to improving our comprehension of the links between molecular structure and effectiveness, the collaboration between machine learning and QSPR research further highlights the potential of computational approaches in drug discovery. This work reveals the mechanisms underlying anti-HIV effectiveness, which paves the way for the development of more potent anti-HIV drugs. This work reveals the mechanisms underlying anti-HIV efficiency, which paves the way for the development of more potent anti-HIV drugs which demonstrates the invaluable advantages of machine learning in assessing drug properties by clarifying the biological processes underlying anti-HIV behavior, which paves the way for the design and development of more effective anti-HIV drugs.

Topical tapinarof is used to treat plaque psoriasis (a skin disease in which red and scaly patches form are appeared on some areas of the body). The goal of the current research is to establish a facile and rapid fluorimetric technique for tapinarof analysis. The approach relied on the reaction between the drug and zinc ion through metal complexation to produce a highly-fluorescent product. The fluorescence was further enhanced by adding sodium dodecyl sulfate, and it was observed at 542 nm following excitation at 497 nm. With a correlation coefficient of 0.9997, the association between emission intensity and tapinarof concentration was linear between 2.0 and 120 ng mL⁻¹. 1.021 ng mL⁻¹ was the quantitation limit while 0.366 ng mL⁻¹ was the detection limit. The buffer type, pH and concentration, type of surfactant and concentration, and finally the diluting solvent were among the reaction conditions that were closely examined and it was found that the optimum conditions were obtained upon employing teorell-stenhagen buffer optimized at pH 6.0, 1.38 × 10^–2 M SDS and distilled water as a solvent are the suitable choice. With great precision and reliability, the drug under study was quantified using this method in ointment formulations. The proposed method's level of greenness was assessed using two methodologies: the analytical greenness metric (AGREE) and the Green Analytical Procedure Index (GAPI), with good recovery results ensuring high efficiency of the proposed approach on analysis of ointment without any interference from additives and excipients.

Recently, phytochemicals play an important role in cancer management. Curcumin (CUR), a natural phytochemical, has been co-administered with widespread chemotherapeutic agents such as doxorubicin (DOX) due to its excellent antitumor activity and the ability to lower the adverse reactions and drug resistance cells associated with DOX use. The present study aims to determine DOX and CUR utilizing a label-free, selective, sensitive, and precise synchronous spectrofluorimetric method. The obvious overlap between the emission spectra of DOX and CUR prevents simultaneous estimation of both analytes by conventional spectrofluorimetry. To solve such a problem, synchronous spectrofluorimetric measurements were recorded at Δλ = 20 nm, utilizing ethanol as a diluting solvent. Curcumin was recorded at 442.5 nm, whereas DOX was estimated at 571.5 nm, each at the zero-crossing point of the other one. The developed method exhibited linearity over a concentration range of 0.04–0.40 μg/mL for CUR and 0.05–0.50 μg/mL for DOX, respectively. The values of limit of detection (LOD) were 0.009 and 0.012 µg/mL, while the values of limit of quantitation (LOQ) were 0.028 and 0.037 µg/mL for CUR and DOX, respectively. The adopted approach was carefully validated according to the guidelines of ICH Q₂R₁. The method was utilized to estimate CUR and DOX in laboratory-prepared mixtures and human biological matrices. It showed a high percentage of recoveries with minimal RSD values. Additionally, three different tools were utilized to evaluate the greenness of the proposed approach.

Purpose

The antibacterial properties of silver nanoparticles (AgNPs) are extensively identified. In large quantities, they might be harmful. So many fields of nanotechnology have shown a great deal of interest in the development of an environmentally friendly, efficient method for synthesizing metal nanoparticles. Because of its antibacterial and antifungal properties toward a wide range of microbes, chitosan silver nanoparticles (AgNPs@Cs) constitute a newly developing class of bio-nanostructured hybrid materials. Furthermore, the use of photothermal therapy (PTT) has been suggested as a means of elimination of germs. These light-stimulated treatments are minimally invasive and have a few side effects. In the present work, the antibacterial effect of AgNPs at low concentrations; prepared by chemical and green methods as antimicrobial and photothermal agents in photothermal therapy; with laser irradiation were explored as combined treatment against MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae.

Methods

Silver nanoparticles were produced in two ways. First, by sodium borohydrides, second, by chitosan (as a natural eco-friendly reducing, and capping agent). The nanostructure of AgNPs and AgNPs@Cs was confirmed by UV–visible spectrometer, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIRs), and direct light scattering (DLS). The antibacterial activity of the prepared nanoparticles and the laser irradiation was tested against three bacterial species of zoonotic importance; MRSA, Pseudomonas aeruginosa, and Klebsiella pneumoniae; and was evaluated by measuring their minimum inhibitory concentrations (MIC).

Results

Silver nanoparticles produced by the two methods had spherical shapes with nearly the same particle size. The analysis of DLS showed that AgNPs were very stable with zeta potential − 28.8 mv, and 47.7 mv by chemical and chitosan synthesis, respectively. Furthermore, AgNPs@Cs showed higher antibacterial activity toward the tested bacterial species than AgNPs by chemical method. Additionally, the bacterial viability using photothermal laser therapy was reduced compared to laser and AgNPs alone. The bactericidal activities were higher when laser diode was coupled with AgNPs@Cs than by chemical reduction.

Conclusion

The laser combined treatment had a higher antimicrobial effect than AgNPs alone or laser irradiation alone.

Worldwide, colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related deaths. Thymidylate synthase (TS) is a crucial component of DNA biosynthesis and has drawn interest as an essential target for cancer treatment. In the current work, we have designed and synthesized twenty-eight new diaryl-based pyrido[2,3-d]pyrimidine/alkyl-substituted pyrido[2,3-d]pyrimidine derivatives and evaluated their anticancer activity against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines cell lines. Additionally, we have carried out TS inhibitory activity and in silico studies for compounds 1n and 2j. All the synthesized compounds exhibited good anticancer activity, but among them, compounds 1n and 2j showed excellent anticancer activity, having IC₅₀ values of 1.98 ± 0.69, 2.18 ± 0.93, 4.04 ± 1.06, and 4.18 ± 1.87 µM; and 1.48 ± 0.86, 3.18 ± 0.79, 3.44 ± 1.51, and 5.18 ± 1.85 µM, against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines respectively with control raltitrexed (IC₅₀ 1.07 ± 1.08, 1.98 ± 0.72, 1.34 ± 1.0, and 3.09 ± 0.96 µM, respectively) and hTS inhibitory activity with IC₅₀ values of 20.47 ± 1.09 and 13.48 ± 0.96 nM with control raltitrexed (IC₅₀ 14.95 ± 1.01 nM). Further, the mechanism of inhibition was revealed by molecular docking, which showed the binding pattern of 1n and 2j to the catalytic site of TS with docking scores of -10.6 and − 9.5 kcal/mol, respectively, with reference raltitrexed (-9.4 kcal/mol). Additionally, the assessment of physicochemical, biochemical, structural, and toxicological characteristics were also in the acceptable range for these compounds. Based on the anticancer activity of compounds, SAR was also performed for lead optimization.

Background

The proposed research study introduces independent concentration extraction (ICE) as a novel UV–Vis spectrophotometric approach. The approach can be used for extracting the concentration of two analytes with severely overlapped spectra from their binary mixtures. ICE is based on spectral extraction platform involving simple smart successive methods that can directly extract the original zero order spectra of the analytes at their characteristic (λ_max). Chlorpheniramine maleate (CPM) and Levocloperastine fendizoate (LCF) are two commonly co-formulated drugs in cough preparations. The combined mixture was used to confirm the validity of the developed ICE tool. Another less green HPTLC was developed for the first time to separate both drugs and help also in confirming the proposed tool.

Methods

For the simultaneous determination of CPM and LCF, two ecologically friendly techniques were employed. The first approach encompasses the use of the ICE spectrophotometric method that could be successively applied for extracting the concentration of two analytes with severely overlapped unresolved spectra in their binary mixtures. Other complementary methods aiming at original spectral extraction; including spectrum subtraction (SS) and unity subtraction (US) were also successfully employed to resolve the zero order spectra of the combined drugs with all their characteristic features and peaks. The second technique used, a high-performance TLC-densitometric one, was performed on silica plates with silica plates F254 and a mobile phase with a ratio of 3:3:3:1 by volume of toluene, ethanol, acetone, and ammonia as a developing system at 230 nm.

Results

The presented extraction approach was executed without any optimization steps or sample pretreatment for the simultaneous determination of CPM and LCF. The method was found to be valid for their determination within concentration range of 3.0–30.0 μg mL⁻¹ for both drugs. For HPTLC method, the resulting R_f values of CPM and LCF were 0.37 and 0.78, within concentration ranges of 0.3–4.0 μg/spot and 0.8–10.0 μg/spot, respectively. Greenness assessment of both developed methodologies showed that the HPTLC method is less green than the spectrophotometric method, yet with comparable sustainability when it comes to the used technique.

Conclusion

The procedures were found to be selective, accurate, and precise for analysis of the studied binary mixture. Furthermore, the environmental impact of the introduced methods was assessed using novel greenness metrics, namely AGREE and Green Analytical Procedure Index (GAPI) to prove their ecological safety. In addition, white analytical chemistry (WAC) evaluation metric was employed to ensure the synergy and coherence of analytical, practical, and ecological attributes.

Due to the lack of other treatment options, a rebirth of polymyxins is urgently required. Colistin (also called polymyxin E) and polymyxin B are the only two examples of this antibiotic class that were effectively employed in such critical situations. In the present work, both of the two studied medications were quantified via a simple, green, and non-extracting spectrophotometric approach based on the formation of ion-pair complexes with Erythrosine B. Without using any organic solvents, the pink color of the created complexes was detected at wavelength = 558 nm. To achieve the highest intensity of absorbance, optimum conditions were established by the screening of many experimental factors such as pH, buffer volume, the volume of Erythrosine B, and the time consumed to undergo the reaction. For Colistin and Polymyxin B respectively, Beer-Lambert’s law was observed at the concentration ranges of 1–6, 1–9 µg mL^− 1. The technique was approved and validated following ICH recommendations. Lastly, the suggested approach has been successfully implemented to quantify the cited medications colorimetrically, for the first time, in their parenteral dosage forms with excellent recoveries. Also, Content uniformity testing was implemented.

HIV is one of the most threatening health conditions with a highly increasing rate, affecting millions of people globally, and from its time of discovery until now, its potential cure cannot be explicitly defined. This challenge of having no/low effective drugs for the subjected virus has called for serious attention in the scientific world of virus disease therapeutics. Most of these drugs yields low effectiveness due to poor delivery; hence, there is a need for novel engineering methods for efficient delivery. In this study, two nanomaterilas (graphene; GP, and fullerene; C60) were modelled and investigated with sulfur (S), selenium (Se), and oxygen (O) atoms, to facilitate the delivery of zidovudine (ZVD). This investigation was computationally investigated using the density functional theory (DFT), calculated at B3LYP functional and Gd3bj/Def2svp level of theory. Results from the frontier molecular orbital (FMO), revealed that the GP/C60_S_ZVD complex calculated the least energy gap of 0.668 eV, thus suggesting a favourable interactions. The study of adsorption energy revealed chemisorption among all the interacting complexes wherein GP/C60_S_ZVD complex (-1.59949 eV) was highlighted as the most interacting system, thereby proving its potential for the delivery of ZVD. The outcome of this research urges that a combination of GP and C60 modified with chalcogen particularly, O, S, and Se can aid in facilitating the delivery of zidovudine.

Background

Facing the significant challenge of overcoming drug resistance in cancer treatment, particularly resistance caused by mutations in epidermal growth factor receptor (EGFR), the aim of our study was to identify potent EGFR inhibitors effective against the ^{T790M/C797S/L858R} mutant, a key player in resistance mechanisms.

Methods

Our integrated in silico approach harnessed machine learning, virtual screening, and activity evaluation techniques to screen 5105 compounds from three libraries, aiming to find candidates capable of overcoming the resistance conferred by the T790M and C797S mutations within EGFR. This methodical process narrowed the search down to six promising compounds for further examination.

Results

Kinase assays identified three compounds to which the T790M/C797S/L858R mutant exhibited increased sensitivity compared to the T790M/L858R mutant, highlighting the potential efficacy of these compounds against resistance mechanisms. Among them, T001-10027877 exhibited dual inhibitory effects, with IC₅₀ values of 4.34 µM against EGFR^{T790M/C797S/L858R} and 1.27 µM against EGFR^T790M/L858R. Further investigations into the antiproliferative effects in H1975, A549, H460 and Ba/F3-EGFR^{L858/T790M/C797S} cancer cells revealed that T001-10027877 was the most potent anticancer agent among the tested compounds. Additionally, the induction of H1975 cell apoptosis and cell cycle arrest by T001-10027877 were confirmed, elucidating its mechanism of action.

Conclusions

This study highlights the efficacy of combining computational techniques with bioactivity assessments in the quest for novel antiproliferative agents targeting complex EGFR mutations. In particular, T001-10027877 has great potential for overcoming EGFR-mediated resistance and merits further in vivo exploration. Our findings contribute valuable insights into the development of next-generation anticancer therapies, demonstrating the power of an integrated drug discovery approach.