Current drug discovery technologies最新文献

Drug-target interactions (DTIs) are an important part of the drug development process. When the drug (a chemical molecule) binds to a target (proteins or nucleic acids), it modulates the biological behavior/function of the target, returning it to its normal state. Predicting DTIs plays a vital role in the drug discovery (DD) process as it has the potential to enhance efficiency and reduce costs. However, DTI prediction poses significant challenges and expenses due to the time-consuming and costly nature of experimental assays. As a result, researchers have increased their efforts to identify the association between medications and targets in the hopes of speeding up drug development and shortening the time to market. This paper provides a detailed discussion of the initial stage in drug discovery, namely drug-target interactions. It focuses on exploring the application of machine learning methods within this step. Additionally, we aim to conduct a comprehensive review of relevant papers and databases utilized in this field. Drug target interaction prediction covers a wide range of applications: drug discovery, prediction of adverse effects and drug repositioning. The prediction of drugtarget interactions can be categorized into three main computational methods: docking simulation approaches, ligand-based methods, and machine-learning techniques.

Background: Ruthenium complexes have shown promise in treating many cancers, including breast cancer. Previous studies of our group have demonstrated the potential of the trans- [Ru(PPh3)2(N,N-dimethylN'-thiophenylthioureato-k2O,S)(bipy)]PF6 complex, the Ru(ThySMet), in the treatment of breast tumor cancers, both in 2D and 3D culture systems. Additionally, this complex presented low toxicity when tested in vivo.

Aims: Improve the Ru(ThySMet) activity by incorporating the complex into a microemulsion (ME) and testing its in vitro effects.

Methods: The ME-incorporated Ru(ThySMet) complex, Ru(ThySMet)_ME, was tested for its biological effects in two- (2D) and three-dimensional (3D) cultures using different types of breast cells, MDAMB- 231, MCF-10A, 4T1.13ch5T1, HMT-3522 and Balb/C 3T3 fibroblasts.

Results: An increased selective cytotoxicity of the Ru(ThySMet)_ME for tumor cells was found in 2D cell culture, compared with the original complex. This novel compound also changed the shape of tumor cells and inhibited cell migration with more specificity. Additional 3D cell culture tests using the non-neoplastic S1 and the triple-negative invasive T4-2 breast cells have shown that Ru(ThySMet)_ME presented increased selective cytotoxicity for tumor cells compared with the 2D results. The morphology assay performed in 3D also revealed its ability to reduce the size of the 3D structures and increase the circularity in T4-2 cells.

Conclusion: These results demonstrate that the Ru(ThySMet)_ME is a promising strategy to increase its solubility, delivery, and bioaccumulation in target breast tumors.

Aim: This research work aimed to design and synthesize some new molecules of phenothiazine. The work's emphasis was on forming new phenothiazines in two series, 1-(10H-phenothiazin- 10-yl)-2-((4-(1-(phenylimino)ethyl)phenyl)amino)ethan-1-one derivatives (4a-4j) and 1-(4-((2-oxo-2- (10H-phenothiazin-10-yl)ethyl)amino)phenyl)-3-phenylprop-2-en-1-one derivatives (P1-P5).

Methods: Chloroacetylation of phenothiazine was done to afford 2-chloro-1-(10H-phenothiazin-10- yl)ethan-1-one, which was further reacted with 4-amino acetophenone to produce 2-((4- acetylphenyl)amino)-1-(10H-phenothiazin-10-yl)ethan-1-one. Then, it was treated with substituted anilines and substituted benzaldehydes to produce the final derivatives 4a-4j and P1-P5, respectively.

Results: All 15 derivatives (4a-4j and P1-P5) were characterized by evaluating their Rf value, melting point, solubility, IR spectroscopy, and ¹HNMR spectroscopy. Molecular docking was performed by using AutoDock Vina v.1.2.0 (The Scripps Research Institute, La Jolla, CA, USA) docking software, and the anxiolytic activity of the derivatives was assessed by using the elevated plus maze model.

Conclusion: The designed scheme was executed in the departmental laboratory. The chemical structure of the compounds was confirmed on the basis of TLC, IR, and ¹HNMR analyses. The docking study revealed a good docking score of the compounds. The Log P value of the compounds indicated their good penetration into CNS. The compounds were also screened for anxiolytic activity. Among them, compounds 4f, 4h, and P3 showed maximum activity as anti-anxiolytic agents.

Background: Nowadays, the majority of the population suffers from the problem of hair loss. It leads to disturbed mental health, lower self-confidence, and a lot more problems. A lot of the hair loss therapies available are not reliable and lead to recurrence and side effects after some time. Cannabinoids (CBD) have recently become quite popular for their benefits against hair loss. CBD oil preparations have been used both internally and externally for oral and topical use, respectively. Due to the presence of the endocannabinoid system (ECS) in the body, which naturally targets CB1 and CB2 receptors, the control of hair fall is possible. CBD is used topically for hair loss, whereas it is administered orally for the treatment and management of a medical condition, i.e., alopecia.

Aim/objective: The present review aimed to provide an in-depth study on hair loss and its management using CBD and its associated mechanisms.

Methods: Electronic databases, such as ScienceDirect, Google Scholar, PubMed, Wiley, Springer, and Scopus, were thoroughly searched for information about how CBD is used, how it works, and what role it plays in treating alopecia and hair loss.

Results: This review has highlighted the use of CBD-based hair loss therapy, and described various types of hair loss and their treatments. This review also details the phytocannabinoids and the potential mechanisms of CBD's activity against hair loss and alopecia.

Conclusion: The data obtained from the literature regarding CBD and hair loss provide a scientific basis for CBD use in alopecia. Additionally, a more precise and comprehensive study concerning CBD needs to be carried out at the pre-clinical and clinical levels.

It is safe to use Curcumin as a cosmetic and therapeutic ingredient in pharmaceutical products. For the uses mentioned above and for fundamental research, it is essential to obtain pure Curcumin from plant sources. There is a requirement for effective extraction and purification techniques that adhere to green chemistry standards for efficiency improvement, process safety, and environmental friendliness. Several outstanding studies have looked into the extraction and purification of Curcumin. This review thoroughly covers the currently available curcumin extraction, synthesis, and transformation techniques. Additionally, Curcumin's poor solubility and low absorption in the human body have limited its potential for pharmaceutical use. However, recent developments in novel curcumin formulations utilizing nanotechnology delivery methods have provided new approaches to transport and maximize the human body's curcumin absorption efficiency. In this review, we explore the various curcumin nanoformulations and the potential medicinal uses of nano curcumin. Additionally, we review the necessary future research directions to recommend Curcumin as an excellent therapeutic candidate.

Introduction: The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. This evaluation covers work reports to define the anticancer activity, the most active synthesized compound for the target, the SAR and, when described, the probable MOA besides similarly considered to deliver complete and target-pointed data for the development of types of anti-tumour medicines of triazine derivatives. Triazine scaffold for the development of anticancer analogues. Triazine can also relate to numerous beneficial targets, and their analogues have auspicious in-vitro and in-vivo anti-tumour activity. Fused molecules can improve efficacy, and drug resistance and diminish side effects, and numerous hybrid molecules are beneath diverse stages of clinical trials, so hybrid derivatives of triazine may offer valuable therapeutic involvement for the dealing of tumours.

Objective: The objective of the recent review was to summarize the recent reports on triazine as well as its analogues with respect to its anticancer therapeutic potential.

Conclusion: The content of the review would be helpful to update the researchers working towards the synthesis and designing of new molecules for the treatment of various types of cancer disease with the recent molecules that have been produced from the triazine scaffold. Triazine scaffolds based on 1,3,5-triazine considerably boost molecular diversity levels and enable covering chemical space in key medicinal chemistry fields.

Background: Several studies have been conducted on 4-H chromene compounds because of their intriguing pharmacological and biological properties. Various new natural compounds having a chromene foundation have been reported over the past 20 years.

Objective: In the present study, we reported the acute oral toxicity, antioxidant activity, and molecular docking study of the most active 4H-chromene derivative2-(4-Bromo-phenoxy)-N-[6-chloro-4-(4- chlorophenyl)-3-cyano-4H-chromen-2-yl]-acetamide (A9).

Method: The acute oral toxicity was carried out as per OECD 423 guidelines. For investigating the antioxidant activity, various biochemical parameters in colon tissue like SOD, CAT, MDA, PC and GSH and also enzyme levels, such as ALT, AST, ALP, and LDH, were measured in this experiment.

Results: Acute oral toxicity study indicated that the A9 ligand was found to be safer in animals. Additionally, the A9 ligand had significant antioxidant properties at various doses and was not found to be harmful to the liver. Due to its stronger binding energy and the appropriate interactions that induce inhibition, the A9 ligand's antioxidant function was also validated by additional molecular docking research.

Conclusion: This compound can be exploited as a lead molecule in further research.

Background: Diabetic foot ulcer (DFU) is a prevalent complication of diabetes that can result in severe consequences. The cost of treating DFUs is high, and there is a lack of new therapies available in developing countries. This has created a demand for complementary and alternative treatments. The objective of this study was to assess the impact of aloe vera gel on the healing process of diabetic foot ulcers.

Materials and methods: The study was a double-blind, randomized, controlled clinical trial. The study samples were 66 patients with diabetic foot ulcers who were randomly assigned to two groups (intervention and control). All ulcers in both groups were washed with normal saline and dressed in sterile gauze. The ulcers in the intervention group were covered with a thin layer of Aloe Vera gel before the dressing. The Bates-Jensen Wound Assessment Tool (BWAT) was used on three occasions, including before the intervention period and at the end of each week. Data were analyzed using SPSS 16.

Results: After three weeks, there was a notable contrast in the recovery pattern of the two groups. The patients who had aloe vera gel added to their dressing showed a more substantial decrease in the mean scores of their BWAT.

Conclusion: These findings are promising and suggest that Aloe vera may be a safe and effective adjunctive treatment for diabetic foot ulcers. However, further research is needed to confirm these results and to investigate the underlying mechanisms of aloe vera's therapeutic effect on diabetic foot ulcers.