Revolutionizing Medicinal Chemistry: The Application of Artificial Intelligence (AI) in Early Drug Discovery.

Artificial intelligence (AI) has permeated various sectors, including the pharmaceutical industry and research, where it has been utilized to efficiently identify new chemical entities with desirable properties. The application of AI algorithms to drug discovery presents both remarkable opportunities and challenges. This review article focuses on the transformative role of AI in medicinal chemistry. We delve into the applications of machine learning and deep learning techniques in drug screening and design, discussing their potential to expedite the early drug discovery process. In particular, we provide a comprehensive overview of the use of AI algorithms in predicting protein structures, drug-target interactions, and molecular properties such as drug toxicity. While AI has accelerated the drug discovery process, data quality issues and technological constraints remain challenges. Nonetheless, new relationships and methods have been unveiled, demonstrating AI's expanding potential in predicting and understanding drug interactions and properties. For its full potential to be realized, interdisciplinary collaboration is essential. This review underscores AI's growing influence on the future trajectory of medicinal chemistry and stresses the importance of ongoing synergies between computational and domain experts.

Polygalic acid inhibits african swine fever virus polymerase activity: findings from machine learning and in vitro testing.

African swine fever virus (ASFV), an extremely contagious virus with high mortality rates, causes severe hemorrhagic viral disease in both domestic and wild pigs. Fortunately, ASFV cannot be transmitted from pigs to humans. However, ongoing ASFV outbreaks could have severe economic consequences for global food security. Although ASFV was discovered several years ago, no vaccines or treatments are commercially available yet; therefore, the identification of new anti-ASFV drugs is urgently warranted. Using molecular docking and machine learning, we have previously identified pentagastrin, cangrelor, and fostamatinib as potential antiviral drugs against ASFV. Here, using machine learning combined with docking simulations, we identified natural products with a high affinity for AsfvPolX proteins. We selected five natural products (NPs) that are located close in chemical space to the six known natural flavonoids that possess anti-ASFV activity. Polygalic acid markedly reduced AsfvPolX polymerase activity in a dose-dependent manner. We propose an efficient protocol for identifying NPs as potential antiviral drugs by identifying chemical spaces containing high-affinity binders against ASFV in NP databases.

Clinicopathologic characteristics and survival of patients with double primary malignancies: breast and colorectal cancer.

PURPOSE: This study aimed to investigate the clinicopathologic features and survival in patients with both breast cancer (BrC) and colorectal cancer (CRC). METHODS: Between 1996 and 2019, patients who were diagnosed with both BrC and CRC were evaluated retrospectively. Patients with distant metastasis, palliative resection, and previous cancer histories except for BrCs or CRCs were excluded. Altogether, 105 patients were divided into the B=C group (n=21), B-first group (n=40), and C-first group (n=44) according to the definition of synchronous and metachronous cancers. The clinicopathologic features and overall survival were evaluated. RESULTS: TNM stages and histologic types were comparable among the 3 groups (P=0.434). The interval of diagnosis was 67.1±40.4 and 59.3±47.2 months in the B- and C-first groups, respectively. The incidence of adjuvant chemotherapy in the B-first group was 57.5%, which was higher than the B=C and C-first groups (P<0.001). The estrogen receptor, progesterone receptor, Ki-67, and HER-2 molecular markers were not significantly different among the groups. The overall survival of the B-first group showed lower survival rates than the C-first group (P=0.039). In the logistic regression, HER-2 status (hazard ratio [HR], 11.9; P=0.032) and lymph node metastasis of CRC (HR, 5.8; P=0.036) were prognostic factors affecting overall survival. CONCLUSION: B-first group had poorer survival outcomes than the C-first group in patients with the metachronous BrC and CRC. HER2 positivity and CRC lymph node metastasis may be prognostic factors that affect overall survival in these patients. The findings support that a colorectal cancer screening program should be included during BrC surveillance.

Agglomeration of galactomannan gum powders: Physical, rheological, and structural characterizations.

Galactomannans (GM), such as guar gum (GG) and locust bean gum (LBG), are extensively used as a thickening agent in the food industry. In this work, the physical, rheological, and structural properties of GG and LBG agglomerated via a fluidized bed agglomerator with different concentrations of maltodextrin (MD) binder were investigated. Agglomerated GM at 40 % MD showed lower Carr index and Hausner ratio, indicating better flowability and lower cohesiveness. The GG showed larger particle sizes than LBG, which was confirmed via SEM images and size distribution profiles. The GM with MD exhibited improved rheological properties. The GG showed lower tan δ values than LBG, indicating the enhancement of their elastic properties. Results exhibit that the physical, rheological, and structural properties of GM can be greatly affected by their agglomerate growths during fluidized bed agglomeration of particles with varying concentrations of MD binder as well as the type of gum.

Photopolymerized Micelle-Laden Hydrogels Can Simultaneously Form and Encapsulate Nanocrystals to Improve Drug Substance Solubility and Expedite Drug Product Design.

Formulation technologies are critical for increasing the efficacy of drug products containing poorly soluble hydrophobic drugs, which compose roughly 70% of small molecules in commercial pipelines. Nanomedicines, such as nanocrystal formulations and amorphous solid suspensions, are effective approaches to increasing solubility. However, existing techniques require additional processing into a final dosage form, which strongly influences drug delivery and clinical performance. To enhance hydrophobic drug product efficacy and clinical throughput, a hydrogel material is developed as a sacrificial template to simultaneously form and encapsulate nanocrystals. These hydrogels contain micelles chemically bound to the hydrogel matrix, where the surfactant structure dictates the crystal size and drug loading. Therefore, nanocrystals can be produced in high yield (up to 90% drug loading, by weight) with precisely controlled sizes as small as 4 nm independently of hydrogel composition. Nanocrystals and surfactant are then released together to increase the solubility up to 70 times above bulk crystalline material. By integrating nanocrystals into a final dosage form, micelle-laden hydrogels simplify hydrophobic drug product design.

Rheological Characteristics of Waxy Rice Starch Modified by Carboxymethyl Cellulose.

The effects of carboxymethyl cellulose (CMC) at different concentrations (0, 0.2, 0.4, and 0.6% w/w) on the rheological properties of waxy rice starch (WRS) pastes were evaluated under both steady and dynamic shear conditions. The flow properties of WRS-CMC mixtures were determined from the rheological parameters of power law and Casson models. All samples demonstrated a clear trend of shear-thinning behavior (n=0.33~0.34), with a marginal difference shown between n values. The addition of CMC to WRS increased the apparent viscosity (ηa,100), consistency index, and Casson yield stress values. The dynamic moduli [storage modulus (G'), loss modulus (G″), and dynamic viscosity (η*)] and ratio of G″/G' values of WRS-CMC mixtures also increased with an increase in CMC concentration; the higher dynamic rheological properties observed at higher CMC concentrations may be attributed to an increase in the viscoelasticity of the continuous phase in the starch-gum mixture system. Dependence of ηa,100 on temperature followed the Arrhenius model for all samples. The Cox-Merz rule was not applicable to WRS-CMC pastes with different CMC concentrations, demonstrating that there was a deviation between η* and steady shear viscosities for all samples. Therefore, the synergistic effect of CMC on the rheological properties of WRS pastes appeared to be the result of coacervation.

Oil Recovery from Micropatterned Triangular Troughs during a Surfactant Flood.

We study the recovery of oil trapped inside micropatterned triangular troughs after injecting a surfactant solution. In our experiments, we track the trapped oil volume with duration of surfactant flood for different capillary numbers. We observe that the capillary number affects the amount of oil recovered as the well as the rate of oil recovery. We employ multiphase flow simulations to analyze our system and show a qualitative agreement between the simulations and experimental results. We also discover that beyond a capillary number, the volume of oil recovered plateaus, and no additional oil is released with an increase in capillary number. We develop a theoretical model to predict the dependence of maximum oil recovery on geometrical features and find that the theoretical predictions compare favorably with the trends obtained from our simulations. Though approximate, theoretical relation provides insights into the efficiency of oil recovery and can be utilized to understand the effect of sharp bends and dead ends in enhanced oil recovery and soil remediation.

Photopatterned oil-reservoir micromodels with tailored wetting properties.

Micromodels with a simplified porous network that represents geological porous media have been used as experimental test beds for multiphase flow studies in the petroleum industry. We present a new method to fabricate reservoir micromodels with heterogeneous wetting properties. Photopatterned, copolymerized microstructures were fabricated in a bottom-up manner. The use of rationally designed copolymers allowed us to tailor the wetting behavior (oleophilic/phobic) of the structures without requiring additional surface modifications. Using this approach, two separate techniques of constructing microstructures and tailoring their wetting behavior are combined in a simple, single-step ultraviolet lithography process. This microstructuring method is fast, economical, and versatile compared with previous fabrication methods used for multi-phase micromodel experiments. The wetting behaviors of the copolymerized microstructures were quantified and demonstrative oil/water immiscible displacement experiments were conducted.