Current Drug Discovery Technologies - Volume 21, Issue 2, 2024

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: Nanoscience and nanotechnology have resulted in the continuous development of new nanomaterials with remarkable properties that make them appealing for pharmaceutical applications. The biocompatibility of metallic nanoparticles is of increasing interest for research scientists currently working towards developing novel nano-based medicines, industrial chemicals, and antigens. There is also a particular interest in using them to counter mutations that up-regulate inflammation enhancers to produce a range of inflammation-related pathologies. Aim: The following review discusses the anti-inflammatory mechanisms of metallic bioconjugated (silver, gold, zinc oxide, titanium dioxide, and selenium) nanoparticles. The current study focuses on nanoparticle manufacturing technologies and the inflammatory response. Methodology: A thorough search was conducted in several databases, including Scopus, Embase, Cochrane, and PubMed. The search terms used included: Alzheimer's disease, mechanism of action, neuroinflammation, the reaction of Mast cells to stress and neuroinflammation. The study included all publications published in English. Results: Green-synthesised nanoparticles can suppress the NF-B and cyclooxygenase-2 pathways, preventing the production of proinflammatory cytokines and ROS scavenging mechanisms. Metallic nanoparticles with anti-inflammatory properties, such as stability and specific targeting, have been briefly discussed. Conclusion: The current research focuses on metallic nanoparticles employed as anti-inflammatory medication molecules, although nanoparticles have applications in various areas (medicine, chemical engineering, and agriculture). Nanoparticles have a large surface-to-volume ratio, which can help them to penetrate cell membranes, and because of their solid ligand-binding capabilities, nanoparticles have been used in the medical treatment of inflammatory pathologies.

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: 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.

Background: Metabolic syndrome is one of the major non-communicable global health hazards of the modern world owing to its amplifying prevalence. Acetyl coenzyme-A carboxylase 2 (ACC 2) is one of the most crucial enzymes involved in the manifestation of this disease because of its regulatory role in fatty acid metabolism. Objective: To find novel potent ACC 2 inhibitors as therapeutic potential leads for combating metabolic syndrome. Methods: In the present study, a two-dimensional quantitative structure-activity relationship (2D QSAR) approach was executed on biologically relevant thiazolyl phenyl ether derivatives as ACC 2 inhibitors for structural optimization. The physiochemical descriptors were calculated and thus a correlation was derived between the observed and predicted activity by the regression equation. The significant descriptors i.e. log P (Whole Molecule) and Number of H-bond Donors (Substituent 1) obtained under study were considered for the design of new compounds and their predicted biological activity was calculated from the regression equation of the developed model. The compounds were further validated by docking studies with the prepared ACC 2 receptor. Results: The most promising predicted leads with the absence of an H-bond donor group at the substituted phenyl ether moiety yet increased overall lipophilicity exhibited excellent amino acid binding affinity with the receptor and showed predicted inhibitory activity of 0.0025 μM and 0.0027 μM. The newly designed compounds were checked for their novelty. Lipinski's rule of five was applied to check their druggability and no violation of this rule was observed. Conclusion: The compounds designed in the present study have tremendous potential to yield orally active ACC 2 inhibitors to treat metabolic syndrome.

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.

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.

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.

Background: The estimated number of cancer cases in India for the year 2022 was found to be 14,61,427. The development of chemotherapeutic agents has reduced the mortality rate, however, they have high toxicity which is a disadvantage. Many researchers have found out that quinolin-2- one possesses anticancer activity, with this background we thought of synthesizing the quinolin-2-one derivatives. Objective: This study aimed to carry out docking, synthesis, characterization, and evaluation of 2-(2- (4-Hydroxy-2-oxoquinolin-1(2H)-yl)phenyl/ substituted phenyl)-3-(phenylamino) thiazolidon-4-one derivatives (IVa-g) as an anticancer agent. Method: Diphenylamine and malonic acid treated with phosphoryl chloride gave compound I, which on formylation afforded compound II, which on reaction with various substituted aromatic phenylhydrazine derivatives gave compounds IIIa-g, which on further reaction with thioglycolic acid and anhydrous zinc chloride yielded the compounds IVa-g. Result: Among all the synthesized novel derivatives, compounds IV a-d showed 50% lysis in the IC50 range of 25-50μg for the A549 cell line, and compounds IVa, and IVb showed 50% lysis in the IC50 range of 25-50μg for the MDA-MB cell line. The compound, 3-((4-fluorophenyl)amino)-2-(2-(4- hydroxy-2-oxoquinolin-1(2H)-yl)phenyl)thiazolidin-4-one (IVg) was found to be the most active against both the cell line, A549 and MDA-MB with IC50 value of 0.0298μmol and 0.0338μmol respectively. The docking results revealed that the synthesized compounds exhibited well-conserved hydrogen bonding with one or more amino acid residues in the active pocket of EGFR tyrosine kinase domain with 4-anilinoquinazoline inhibitor erlotinib (PDB ID:1M17). Compound IVg showed the highest MolDock score of -137.813 compared to the standard drug Imatinib having a MolDock score of -119.354. Conclusion: Compound IVg showed the highest MolDock score and was also found to be most potent against both the cell line, A549, and MDA-MB.

Background: Bisphenol A (BPA) is a known neurotoxic compound with potentially harmful effects on the nervous system. Cyanidin (CYN) has shown promise as a neuroprotective agent. Objective: The current study aims to determine the efficacy of CYN against BPA-induced neuropathology. Methods: In vitro experiments utilized PC12 cells were pre-treated with gradient doses of CYN and further stimulated with 10ng/ml of BPA. DPPH radical scavenging activity, catalase activity, total ROS activity, and nitric oxide radical scavenging activity were done. In vivo assessments employed doublecortin immunohistochemistry of the brain in BPA-exposed Sprague-Dawley rats. Further, In silico molecular docking of CYN with all proteins involved in canonical Wnt signaling was performed using the Autodock v4.2 tool and BIOVIA Discovery Studio Visualizer. Results: IC50 values of CYN and ascorbic acid were determined using dose-response curves, and it was found to be 24.68 ± 0.563 μg/ml and 20.69 ± 1.591μg/ml, respectively. BPA-stimulated cells pre-treated with CYN showed comparable catalase activity with cells pre-treated with ascorbic acid (p = 0.0287). The reactive species production by CYN-treated cells was significantly decreased compared to BPA-stimulated cells (p <0.0001). Moreover, CYN significantly inhibited nitric oxide production compared to BPA stimulated and the control cells (p < 0.0001). In vivo CYN positively affected immature neuron quantity, correlating with dosage. During molecular docking analysis, CYN exhibited a binding affinity > -7 Kcal/mol with all the key proteins associated with the Wnt/β- catenin signaling cascade. Conclusion: Conclusively, our finding suggests that CYN exhibited promise in counteracting BPAinduced oxidative stress, improving compromised neurogenesis in hippocampal and cortical regions, and displaying notable interactions with Wnt signaling proteins. Thereby, CYN could render its neuroprotective potential against BPA-induced neuropathology.