Current Drug Discovery Technologies - Volume 22, Issue 3, 2025

The Paeoniaceae family contains only the Paeonia genus and is considered a major group of flowering plants. Several traditional and pharmacological applications of Paeoniaceae herbs have been described. This paper aimes to determine the pharmacological activities of the most prevalent herbs from the genus Paeonia by focusing on their underlying mechanism of action and signaling pathways, providing insight for further in-depth research on the medicinal resources of Paeonia.

The “Paeoniaceae” keyword was searched from 1^st January 1995 to 15^th May 2024 through the PubMed and Scopus databases. Only papers related to pharmacology, pharmaceutics, and toxicology were extracted. The possible pharmacological activity of the Paeonia plants, including their underlying mechanisms of action and signaling pathways, was subsequently discussed.

Following our venture, only 15 Paeonia herbs were adequately evaluated for their pharmacological applications. Paeonia lactiflora Pall., Paeonia suffruticosa Andrews, and Paeonia emodi Royle are among the most prevalent Paeonia plants that have attracted increased attention in modern pharmacological studies. Paeonia herbs possess various pharmacological applications, such as anti-inflammatory, anti-allergic, anticancer, antimicrobial, cardiovascular protective, cosmetic and skincare, radical scavenging, hepatoprotective and anti-ulcerative, anti-diabetic, musculoskeletal, and neuroprotective effects, and can be used as alternative therapies under critical medical conditions.

Among the applications of Paeonia herbs, anti-inflammatory and antioxidant activities are critical, as most other pharmacological effects are attributed to them. In other words, nuclear factor (NF)-κB and nuclear factor erythroid 2-related factor 2 (Nrf2) can be considered the most important signaling pathways involved in the pharmacological activity of Paeonia herbs.

Computer-aided Drug Design (CADD) approaches are essential in the drug discovery and development process. Pharmaceutical and biotechnology organizations, as well as academic institutions, utilize CADDs to identify and enhance the efficacy of bioactive compounds.

This study aims to entice researchers by investigating the significance or value of Computer-aided Drug and Design (CADD) and its fundamental principles. The main focus is to speed up the drug discovery process, improve accuracy, and reduce the time and financial resources needed, ultimately making a positive impact on public health.

A comprehensive literature search was conducted using databases such as PubMed and Scopus, focusing on studies published till 2024. The selection of studies was based on their analysis of the connection between contemporary pharmaceutical research and computer-aided drug design, with a focus on both structure-based and ligand-based drug design strategies can include molecular docking, fragment-based drug discovery, de novo drug design, pharmacophore modelling, Quantitative structure-activity relationship, 3D-QSAR, homology modelling, in silico absorption–distribution–metabolism–excretion–toxicity, and machine learning/deep learning.

Computer-aided Drug Design (CADD) approaches are mathematical tools used to modify and measure certain characteristics of possible drug candidates. These methods are implemented in various applications. These encompass a variety of software products that are accessible to the public and can be purchased for corporate use. The CADD method is used at several stages of the drug development process, including as a foundation for chemical synthesis and biological testing. It provides information for the development of future SAR (Structure-Activity Relationship), resulting in enhanced molecules in terms of their activity and ADME (Absorption, Distribution, Metabolism, and Excretion). CADD techniques are predominantly employed to analyze and assess the affinity of large molecules for specific biomolecules, such as DNA, RNA, proteins, and enzymes, which serve exclusively as receptors. CADD improves the selection of lead compounds by predicting various parameters, including drug-likeness, physicochemical properties, pharmacokinetics, and toxicity. The application of CADD in drug modelling is to tackle challenges such as cost and time constraints. Modern computer-assisted drug discovery necessitates conducting virtual screening and high-throughput screening (HTS).

Computer-aided drug design plays a crucial role for academic institutions and leading pharmaceutical companies in the development of drugs that enhance potency with the significance of reducing both time and costs.

The development of antimicrobial agents is crucial for several reasons, primarily to combat infectious diseases and to address the growing threat of antimicrobial resistance. The need for the continued development of antimicrobial drugs persists despite the presence of many existing drugs for several reasons, viz emerging new pathogens and diseases, resistance to existing drugs, and propagation of multidrug resistance to existing drugs.

The objective of the study was to synthesize and evaluate the antimicrobial potential of newly synthesized benzothiazole derivatives.

A new series of 2-(substituted amino)-N-(6-substituted-1,3-benzothiazol-2yl)acetamide BTC(a-t) has been synthesized by reacting it with chloracetyl chloride with substituted 2-amino benzothiazole and further refluxed with various substituted amines to obtain target compounds. The synthesized compounds were screened experimentally for their antimicrobial property against gram-positive and gram-negative bacteria and fungi. The zone of inhibition and minimum inhibitory concentration of compounds were determined against selected bacterial and fungal strains. Further docking study was carried out to check the probable interactions with the selected protein using V-life MDS 3.5 software (DNA gyrase, PDB: 3G75).

Compounds BTC-j N-(6-methoxy-1,3-benzothiazol-2-yl)-2-(pyridine-3-ylamino)acetamide and BTC-r N-(6-nitro-1,3-benzothiazol-2-yl)-2-(pyridine-3-ylamino)acetamide were found to have good antimicrobial potential. The compound BTC-j showed good antibacterial activity against S. aureus at an MIC value of 12.5 µg/mL, B. subtilis at MIC of 6.25µg/mL, E. coli at MIC of 3.125µg/mL, and P. aeruginosa at MIC of 6.25µg/mL. Thus, from the result, it was observed that compounds BTC-j, BTC-f, BTC-n, and BTC-r exhibited significant antibacterial and antifungal potential at different concentrations.

The present study resulted in the successful synthesis of 2-acetamido substituted benzothiazole derivatives BTC(a-t) with good yields. The dock score of the compounds and the antimicrobial activity were found to be consistent. No statistical difference in the antimicrobial activity of the standard and test compounds was found, indicating that the test compounds have comparable activity. Therefore, benzothiazole linked to heterocyclic rings with an acetamide linkage may serve as promising lead molecules for further optimization in the journey to discover potent antibacterial agents. Thus, we conclude that the synthesized compounds have the potential for further development as novel antimicrobial agents.

Human Immunodeficiency Virus (HIV) is a retrovirus with single-stranded RNA that leads to the challenging disease of acquired immunodeficiency syndrome (AIDS). Combination antiretroviral therapy (cART) can prevent the progression of the disease, but it is not capable of long-term HIV elimination. One of the significant obstacles to treating HIV-1-infected individuals is the creation of latent cell reservoirs early in the infection. Gene-based therapies that utilize RNA interference (RNAi) to silence host or viral gene expression are considered promising therapeutic approaches. It has been demonstrated that RUNX1, a T-cell-specific transcription factor, may significantly affect HIV replication and infection. According to accumulating evidence on the role of interfering RNA techniques in inhibiting gene expression and considering the role of RUNX1 in the replication of HIV-1. In this study, we aim to design shRNAs against RUNX1 that can target the replication of HIV-1.

Several computational methods, including target alignment, similarity search, and secondary structure prediction, have been employed in the design of shRNA against RUNX1.

Seven shRNA molecules with the highest efficiency were designed and validated using computational methods to silence the RUNX1 gene.

In the present study, we designed shRNA against RUNX1, which can target latent cells infected with HIV. Suppression of RUNX1 by shRNA reactivates HIV in the latent cells and subsequently potentiates the immune response toward identifying accurate virus-infected cells. This process may lead to an effective and efficient reduction of the volume of cell reservoirs infected with HIV.

Thymus atlanticus (Ball) Roussine is a Moroccan endemic thyme species that is traditionally used as an aromatic and medicinal plant. Several studies have demonstrated its pharmacological significance and therapeutic value.

The current study aimed to assess the vasorelaxant effect of the aqueous extract of this species.

The contractility of isolated rat aortas was investigated using the multi-well organ bath technique. This method was adapted and validated in our experimental conditions using epinephrine and hydralazine as vasoconstrictive and vasodilator agents, respectively. The application of 10 µM epinephrine induced a clear vasoconstriction of the aorta rings (Lumen reduction = 31.8±0.4%). However, hydralazine induced a dose-dependent relaxation with an EC50 value of 6.1±1.2 mM. For the aqueous extract of T. atlanticus, the aortic rings were precontracted with epinephrine, and then increasing concentrations (0.125-1 mg/mL) of this extract were added cumulatively.

The results have indicated T. atlanticus extract to have a significant vasodilatory effect in a dose-dependent manner (EC50 = 0.52±0.03 mg/mL).

The findings provide preliminary evidence of the vasorelaxant effect of the aqueous extract of T. atlanticus using a low-cost optical approach. However, the cellular and molecular mechanisms underlying this effect have yet to be revealed.

Clopidogrel, an antiplatelet drug commonly used in cardiovascular disease, is metabolized by the liver mainly through CYP2C19. Concomitant use of Proton pump inhibitors along with clopidogrel may affect the potency of clopidogrel by CYP2C19 inhibition. However, a novel PPI, ilaprazole is known to differ in its pharmacokinetic features, given the potential differences between ilaprazole’s interactions and their metabolism with clopidogrel. Network pharmacology investigation could be a useful tool to evaluate the drug-drug interaction between them.

The molecular structures and targets were retrieved from PubChem and SwissTargetPrediction to establish the information related to the identified drugs. The possible shared targets between the clopidogrel and PPIs were explored by a Venn analysis. Subsequently, Protein-Protein Interaction networks were established using the STRING database. Hub genes were also determined using the Cytoscape cytoHubba plugin.

Ilaprazole (13.6%) and pantoprazole (13.6%) were characterized by fewer targets being shared with clopidogrel compared to conventional PPIs (14.9%). Moreover, CYP2C19 was not a hub gene in ilaprazole and pantoprazole interactions, which indicated no significant CYP2C19 involvement. On the other hand, CYP2C19 functioned as a hub gene in the interactions with rabeprazole, lansoprazole, dexlansoprazole, omeprazole, and esomeprazole. As a result, patients receiving pantoprazole and ilaprazole would be at a lower risk for developing adverse cardiovascular events by maintaining the clopidogrel therapeutic effect.

The application of the network pharmacology technique allows us to consider the potential for different effects of PPIs on clopidogrel and its metabolism via CYP2C19. There is a lower chance of experiencing adverse effects from an interaction between ilaprazole and clopidogrel as ilaprazole has not been linked to CYP2C19. More research is necessary to confirm these results and provide clinical guidance for patients undergoing clopidogrel and PPI combination therapy.