Development Of Innovative Drugs Research Articles

The development of innovative therapeutic drugs targeting hypoxia responses

The 2019 Nobel Prize in Physiology or Medicine was awarded to Dr. William G. Kaelin Jr, Dr. Peter J. Ratcliffe, and Dr. Gregg L. Semenza for their elucidation of new physiological mechanisms "How cells sense and adapt to oxygen availability". Moreover, two different drugs, HIF-PH inhibitors and HIF-2 inhibitors were also developed based on the discovery. Interestingly, those three doctors have different backgrounds as a medical oncologist, a nephrologist, and a pediatrician, respectively. They have started the research based on their own unique perspectives and eventually merged as "the elucidation of the response mechanism of living organisms to hypoxic environments". In this review, we will explain how the translational research that has begun to solve unmet clinical needs successfully contributed to the development of innovative therapeutic drugs.

Biomedical and Biotechnological Potential of Animal Venoms: Bothrops Snake Venoms and their Antimicrobial Applications.

The pursuit of novel treatment alternatives to address the accumulated resistance to antimicrobials over the years has prompted the scientific community to explore biodiversity, particularly animal venom, as a potential source of new antimicrobial drugs. Snake venoms, with their complex mixtures of components, are particularly promising targets for investigation in this regard. The search for novel molecules exhibiting antimicrobial activity against multidrug-resistant strains is of paramount importance for public health and numerous research groups worldwide. High expectations within the healthcare field are supported by the scientific literature, which highlights the potential development of innovative drugs through in vivo and in vitro application, depending on dose titration. Snake venoms and their molecules and peptides offer exponential possibilities for biotechnological applications as antimicrobial agents. However, many uncertainties and unexplored avenues remain, presenting opportunities for discoveries and research.

Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.

Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.

Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment.

The extracellular matrix (ECM) is a complex three-dimensional structure composed of proteins, glycans, and proteoglycans, constituting a critical component of the tumor microenvironment. Complex interactions among immune cells, extracellular matrix, and tumor cells promote tumor development and metastasis, consequently influencing therapeutic efficacy. Hence, elucidating these interaction mechanisms is pivotal for precision cancer therapy. T lymphocytes are an important component of the immune system, exerting direct anti-tumor effects by attacking tumor cells or releasing lymphokines to enhance immune effects. The ECM significantly influences T cells function and infiltration within the tumor microenvironment, thereby impacting the behavior and biological characteristics of tumor cells. T cells are involved in regulating the synthesis, degradation, and remodeling of the extracellular matrix through the secretion of cytokines and enzymes. As a result, it affects the proliferation and invasive ability of tumor cells as well as the efficacy of immunotherapy. This review discusses the mechanisms underlying T lymphocyte-ECM interactions in the tumor immune microenvironment and their potential application in immunotherapy. It provides novel insights for the development of innovative tumor therapeutic strategies and drug.

Abstract LB216: Static and microfluidic platforms for novel therapeutic testing in high-grade serous ovarian cancer

Abstract Background: High-Grade Serous Ovarian Cancer (HGSOC) is the most lethal OC type because of its silent progression and lack of specific markers for early detection. In this context, the timely initiation of effective treatment is imperative to prevent disease progression extending life expectancy. However, responses to treatment can vary significantly among individuals, presenting clinical challenges in selecting effective treatments, necessitating the interpretation of molecular and genomic data of the patient on a case-by-case basis. The aim of this study is to establish a highly sensitive platform, implemented with microfluidic technology, to predict patient drug responses with the goal of assisting oncologists in shaping effective treatments. Moreover, validating this platform through a retrospective study, enabling the development of innovative drugs. Methods: In this work, patient-derived ovarian cancer organoids (PDOs) were engineered for drug screening and twenty FDA approved drugs were assessed on seven PDOs derived from both primary tumors and ascites. The fidelity of PDOs in reproducing the histopathology of the primary tumour was confirmed by immunohistochemistry. Proteomics and repeated screening on high- and low-passage PDOs confirmed the reliability of the platform over time. Furthermore, to bridge the gap between static systems and the dynamic of human tumours, a microfluidic platform was employed and using fluorescence microscopy the patients' drug sensitivity was predicted (PMID: 37143603). Results: PDOs were able to replicate patients' response to the drug in a retrospective study and surprisingly, in some cases, to predict resistance to certain drugs administered on the basis of strong, clinically validated predictive biomarkers, which proved ineffective in the clinic. The platform could predict innovative therapeutic strategies as demonstrated by inhibiting the activity of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), a novel druggable target for OC (PMID: 22322860, 29746956, 30697729). The Pin1 inhibitor (VS10) is effective in a subset of patients resistant to platinum-based chemotherapy and synergize with doxorubicin. Finally, a microfluidic platform fluorescence based, which improved drug penetration in PDOs was developed for efficient and faster drug screening. Conclusions: This study underscores the significance of utilizing engineered PDOs to develop predictive and easy to use platforms that can truly aid oncologists in devising patient-specific treatments while circumventing the use of drugs that, despite strong recommendations, may prove ineffective. Furthermore, these platforms have demonstrated their effectiveness in the development of innovative therapeutics, such as Pin1 inhibitors, which have been proven both effective and safe in animal models, underscoring the need for clinical studies. Acknowledgments: AIRC IG23566 Citation Format: Enrico Cavarzerani, Gloria Saorin, Matteo Mauceri, Isabella Caligiuri, Michele Bartoletti, Vincenzo Canzonieri, Flavio Rizzolio. Static and microfluidic platforms for novel therapeutic testing in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB216.

A new era in the science and care of kidney diseases.

Notable progress in basic, translational and clinical nephrology research has been made over the past five decades. Nonetheless, many challenges remain, including obstacles to the early detection of kidney disease, disparities in access to care and variability in responses to existing and emerging therapies. Innovations in drug development, research technologies, tissue engineering and regenerative medicine have the potential to improve patient outcomes. Exciting prospects include the availability of new drugs to slow or halt the progression of chronic kidney disease, the development of bioartificial kidneys that mimic healthy kidney functions, and tissue engineering techniques that could enable transplantable kidneys to be created from the cells of the recipient, removing the risk of rejection. Cell and gene therapies have the potential to be applied for kidney tissue regeneration and repair. In addition, about 30% of kidney disease cases are monogenic and could potentially be treated using these genetic medicine approaches. Systemic diseases that involve the kidney, such as diabetes mellitus and hypertension, might also be amenable to these treatments. Continued investment, communication, collaboration and translation of innovations are crucial to realize their full potential. In addition, increasing sophistication in exploring large datasets, implementation science, and qualitative methodologies will improve the ability to deliver transformational kidney health strategies.

Design, synthesis and characterization of ethyl 3-benzoyl-7-morpholinoindolizine-1-carboxylate as anti-tubercular agents: In silico screening for possible target identification.

A thorough search for the development of innovative drugs to treat tuberculosis, especially considering the urgent need to address developing drug resistance, we report here a synthetic series of ethyl 3-benzoyl-7-morpholinoindolizine-1-carboxylate analogues (5a-o) as potent anti-tubercular agents. These morpholino-indolizines were synthesized by reacting 4-morpholino pyridinium salts, with various electron-deficient acetylenes to afford the ethyl 3-benzoyl-7-morpholinoindolizine-1-carboxylate analogues (5a-o). All synthesized intermediate and final compounds are characterized by spectroscopic methods such as 1H NMR, 13C NMR and HRMS and further examined for their anti-tubercular activity against the M. tuberculosis H37Rv strain (ATCC 27294-American type cell culture). All the compounds screened for anti-tubercular activity in the range of 6.25-50 μM against the H37Rv strain of Mycobacterium tuberculosis. Compound 5g showed prominent activity with MIC99 2.55 μg/mL whereas compounds 5d and 5j showed activity with MIC99 18.91 μg/mL and 25.07 μg/mL, respectively. In silico analysis of these compounds revealed drug-likeness. Additionally, the molecular target identification for Malate synthase (PDB 5CBB) is attained by computational approach. The compound 5g with a MIC99 value of 2.55 μg/mL against M. tuberculosis H37Rv emerged as the most promising anti-TB drug and in silico investigations suggest Malate synthase (5CBB) might be the compound's possible target.

Comparison of the Expedited Programs for Innovative Drug Development and Approval among United States, European Union, and Republic of Korea

Comparison of the Expedited Programs for Innovative Drug Development and Approval among United States, European Union, and Republic of Korea

Curculigoside Attenuates Endoplasmic Reticulum Stress-Induced Epithelial Cell and Fibroblast Senescence by Regulating the SIRT1-P300 Signaling Pathway.

The senescence of alveolar epithelial cells (AECs) and fibroblasts plays a pivotal role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a condition lacking specific therapeutic interventions. Curculigoside (CCG), a prominent bioactive constituent of Curculigo, exhibits anti-osteoporotic and antioxidant activities. Our investigation aimed to elucidate the anti-senescence and anti-fibrotic effects of CCG in experimental pulmonary fibrosis and delineate its underlying molecular mechanisms. Our findings demonstrate that CCG attenuates bleomycin-induced pulmonary fibrosis and lung senescence in murine models, concomitantly ameliorating lung function impairment. Immunofluorescence staining for senescence marker p21, alongside SPC or α-SMA, suggested that CCG's mitigation of lung senescence correlates closely with the deceleration of senescence in AECs and fibroblasts. In vitro, CCG mitigated H2O2-induced senescence in AECs and the natural senescence of primary mouse fibroblasts. Mechanistically, CCG can upregulate SIRT1 expression, downregulating P300 expression, enhancing Trim72 expression to facilitate P300 ubiquitination and degradation, reducing the acetylation levels of antioxidant enzymes, and upregulating their expression levels. These actions collectively inhibited endoplasmic reticulum stress (ERS) and alleviated senescence. Furthermore, the anti-senescence effects and mechanisms of CCG were validated in a D-galactose (D-gal)-induced progeroid model. This study provides novel insights into the mechanisms underlying the action of CCG in cellular senescence and chronic diseases, offering potential avenues for the development of innovative drugs or therapeutic strategies.

Abstract 5815: Next-generation RNAi therapeutics: siRNA-loaded exosomes targeting KRAS G12C in non-small cell lung cancer (NSCLC)

Abstract Background: NSCLC represents the predominant subtype of lung cancer, boasting an overall 5-year survival rate of 26%, a figure that fluctuates based on the disease stage. Within NSCLC, certain cancer gene mutations, notably KRAS G12C, are currently classified as 'undruggable targets,' creating hurdles in achieving effective treatment. The development of innovative anticancer drugs aimed at these challenging targets is expected to present a viable solution to these difficulties. Methods: Exosomes have garnered attention as an inventive drug delivery system for in vivo gene delivery through systemic injection. We used a new post-loading approach by actively loading KRAS G12C siRNA into exosomes using the shock waves (SWEET: shock wave exosome engineering technology ) in this study. The effect of in vitro and in vivo were tested in NCI-H358 (KRAS G12C mt NSCLC) cells and its xenograft mouse model. The tumor size and weight were measured twice a week. Results: We developed an exosome-based therapeutic using siRNA to effectively inhibit KRAS G12C, targeting NSCLC. The SWEET platform's post-loading method showed a high efficiency in loading KRAS G12C siRNA into exosomes. The KRAS G12C siRNA-loaded exosomes effectively silenced oncogenic KRAS G12C expression in cancer cells; they inhibited tumor growth when administered intravenously in a NSCLC xenograft mouse model. Remarkably, the anticancer effect of KRAS G12C-loaded exosome was similar to that of Sotorasib, a KRAS G12C mutation targeting anti-cancer drug. Conclusion: Our study showed KRAS G12C siRNA loaded exosomes were effectively delivered to NSCLC tumor tissue via intravenous (IV) administration. And its anti-cancer effects were very similar to sotorasib, showing potential as a treatment for KRAS G12C mutation-expressing cancer. The effective delivery of siRNA to tumor tissues through exosomes highlights the potential of this technology as a promising approach for developing new RNAi therapeutics for cancer. Citation Format: Hyo Kyeong Kim, Yujeong Choi, Kyoung Hwa Kim, Yeongju Byun, Tae Hee Kim, Jae Hwan Kim, Shung Hyun An, DaeHo Bae, MyeongKwan Choi, Jihwa Chung, Kihwan Kwon. Next-generation RNAi therapeutics: siRNA-loaded exosomes targeting KRAS G12C in non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5815.

Bacteroides and NAFLD: pathophysiology and therapy.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition observed globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Currently, the US Food and Drug Administration (FDA) has not approved any drugs for the treatment of NAFLD. NAFLD is characterized by histopathological abnormalities in the liver, such as lipid accumulation, steatosis, hepatic balloon degeneration, and inflammation. Dysbiosis of the gut microbiota and its metabolites significantly contribute to the initiation and advancement of NAFLD. Bacteroides, a potential probiotic, has shown strong potential in preventing the onset and progression of NAFLD. However, the precise mechanism by which Bacteroides treats NAFLD remains uncertain. In this review, we explore the current understanding of the role of Bacteroides and its metabolites in the treatment of NAFLD, focusing on their ability to reduce liver inflammation, mitigate hepatic steatosis, and enhance intestinal barrier function. Additionally, we summarize how Bacteroides alleviates pathological changes by restoring the metabolism, improving insulin resistance, regulating cytokines, and promoting tight-junctions. A deeper comprehension of the mechanisms through which Bacteroides is involved in the pathogenesis of NAFLD should aid the development of innovative drugs targeting NAFLD.

Challenges and advancements in high-throughput screening strategies for cancer therapeutics

Drug discovery relies on high-throughput screening (HTS) methods incorporating both target- and cell-based assays. This comprehensive review delves into the challenges and benefits associated with these assays within the context of HTS. The strategies for developing screening assays, spanning both primary and secondary screens for target identification, are discussed. Furthermore, we review the methods of identifying the most efficacious drugs through these approaches for the treatment of cancer in detail. While various drugs have been identified for cancer treatment, there remains a pressing need for more relevant phenotypic assays. These assays aim to produce the desired disease phenotype, with a specific emphasis on highlighting targets rather than off-targets. The ultimate goal is to pave the way for innovative drug development strategies that can effectively treat cancer patients, thereby reducing the mortality rate.

Influence of DNA Methylation on Vascular Smooth Muscle Cell Phenotypic Switching.

Vascular smooth muscle cells (VSMCs) are crucial components of the arterial wall, controlling blood flow and pressure by contracting and relaxing the artery walls. VSMCs can switch from a contractile to a synthetic state, leading to increased proliferation and migratory potential. Epigenetic pathways, including DNA methylation, play a crucial role in regulating VSMC differentiation and phenotypic flexibility. DNA methylation involves attaching a methyl group to the 5' carbon of a cytosine base, which regulates gene expression by interacting with transcription factors. Understanding the key factors influencing VSMC plasticity may help to identify new target molecules for the development of innovative drugs to treat various vascular diseases. This review focuses on DNA methylation pathways in VSMCs, summarizing mechanisms involved in controlling vascular remodeling, which can significantly enhance our understanding of related mechanisms and provide promising therapeutic approaches for complex and multifactorial diseases.

Pancreatic Cancer Treatment Targeting the HGF/c-MET Pathway: The MEK Inhibitor Trametinib.

Pancreatic cancer is characterized by fibrosis/desmoplasia in the tumor microenvironment, which is primarily mediated by pancreatic stellate cells and cancer-associated fibroblasts. HGF/c-MET signaling, which is instrumental in embryonic development and wound healing, is also implicated for its mitogenic and motogenic properties. In pancreatic cancer, this pathway, along with its downstream signaling pathways, is associated with disease progression, prognosis, metastasis, chemoresistance, and other tumor-related factors. Other features of the microenvironment in pancreatic cancer with the HGF/c-MET pathway include hypoxia, angiogenesis, metastasis, and the urokinase plasminogen activator positive feed-forward loop. All these attributes critically influence the initiation, progression, and metastasis of pancreatic cancer. Therefore, targeting the HGF/c-MET signaling pathway appears promising for the development of innovative drugs for pancreatic cancer treatment. One of the primary downstream effects of c-MET activation is the MAPK/ERK (Ras, Ras/Raf/MEK/ERK) signaling cascade, and MEK (Mitogen-activated protein kinase kinase) inhibitors have demonstrated therapeutic value in RAS-mutant melanoma and lung cancer. Trametinib is a selective MEK1 and MEK2 inhibitor, and it has evolved as a pivotal therapeutic agent targeting the MAPK/ERK pathway in various malignancies, including BRAF-mutated melanoma, non-small cell lung cancer and thyroid cancer. The drug's effectiveness increases when combined with agents like BRAF inhibitors. However, resistance remains a challenge, necessitating ongoing research to counteract the resistance mechanisms. This review offers an in-depth exploration of the HGF/c-MET signaling pathway, trametinib's mechanism, clinical applications, combination strategies, and future directions in the context of pancreatic cancer.

Unlocking translational machinery for antitubercular drug development

Targeting translational factor proteins presents significant promise for the development of innovative antitubercular drugs. Previous insights from antibiotic binding mechanisms and recently solved 3D crystal structures of Mycobacterium tuberculosis (Mtb) elongation factor thermo unstable–GDP (EF-Tu–GDP), elongation factor thermo stable–EF-Tu (EF-Ts–EF-Tu), and elongation factor G–GDP (EF-G–GDP) have opened up new avenues for the design and development of potent antituberculosis (anti-TB) therapies.

Potential of Surface Functionalized Nanomaterials in Innovative Drug Development: A Mini-review

Abstract: The unique properties of nanomaterials (NMs) make them special entities for biomedical innovation and research. Early diagnosis and follow-up of diseases are easily possible with the help of nanotechnology and nanomedicine, which can help combat any medical condition. Surface functionalization with specific molecules might impart marked properties to NMs, leading to the modification of cellspecific interactions within the biological systems. This modification may provide excellent phenomena for innovative drug development. Modified NMs might play essential roles in various applications, i.e., in vivo diagnostics, magnetic resonance imaging (MRI), positron emission tomography (PET), etc. Functionalization of NMs with appropriate ligands, small molecules, or polymers assigned them enhanced stability, biocompatibility, and functionality for their novel and improved biological applications. Surface functionalized NMs might display enhanced antimicrobial, antidiabetic, and drug delivery potential for various applications. Different studies reported the potential of functionalized metallic nanoparticles in regenerative medicines. Conjugation of NMs with various molecules such as peptides, small ligands, polysaccharides, proteins, saturated and polyunsaturated fatty acids, siRNA, plasmids, and DNA, might be achieved by various reactions. Biomolecule-conjugated nanoparticles result in the production of hybrid NMs with specific and novel biological interactions in biological systems. Chemical treatment methods are considered among the most trusted and efficient functionalization methods. Some commonly used techniques and strategies of functionalization involve grafting to and grafting from methods, ligand exchange technique, covalent bonding, chemisorption, non-covalent interactions, electrostatic adsorption, etc. This brief review is dedicated to the surface functionalization of NMs with the latest development

Alpha-sitosterol: a new antiviral agent produced by Streptomyces misakiensis and its potential activity against Newcastle disease virus

BackgroundNewcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated.Resultsα-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P < 0.0001) inhibited after α-sitosterol treatment. There was a significant (P < 0.0001) decrease in the log 2 of HA activity, with values of − 0.500 (75%, chicken RBCs) before inoculation in SPF-ECEs and − 1.161 (50%, RBCs) and − 1.403 (75%, RBCs) following SPF-ECE inoculation. Compared to ECEs inoculated with NDV alone, the α-sitosterol-treated group showed improvement in histological lesion ratings for chorioallantoic membranes (CAM) and hepatic tissues. The CAM of the α-sitosterol- inoculated SPF-ECEs was preserved. The epithelial and stromal layers were noticeably thicker with extensive hemorrhages, clogged vasculatures, and certain inflammatory cells in the stroma layer in the NDV group. However, mild edema and inflammatory cell infiltration were observed in the CAM of the treated group. ECEs inoculated with α-sitosterol alone showed normal histology of the hepatic acini, central veins, and portal triads. Severe degenerative alterations, including steatosis, clogged sinusoids, and central veins, were observed in ECEs inoculated with NDV. Mild hepatic degenerative alterations, with perivascular round cell infiltration, were observed in the treated group.ConclusionTo the best of our knowledge, this is the first study to highlight that the potentially bioactive secondary metabolite, α-sitosterol, belonging to the terpene family, has the potential to be a biological weapon against virulent NDV. It could be used for the development of innovative antiviral drugs to control NDV after further clinical investigation.

A Comprehensive Review of Abroma Augusta (Devil's Cotton): Phytochemical Constituents, Ethnomedicinal Applications, and Pharmacological Properties

Abstract: The nutritional and therapeutic potential of medicinal plants is constantly being investigated. This is especially relevant in today's world, where an increasing number of people are turning to complementary and alternative therapies to address their health-related concerns. Traditional knowledge, as a valuable resource, plays a crucial role in the development of new herbal medicines. Abroma augusta stands out as one such medicinal plant that has a rich history of use in traditional medicine. It has been employed to address a wide spectrum of health issues, including diabetes, menstrual irregularities, respiratory problems, musculoskeletal disorders, urinary ailments, and sexual dysfunctions, among others. While various parts of this plant species are believed to possess pharmacological properties, the active compounds and underlying mechanisms remain largely unexplored. To facilitate the development of innovative drugs for the benefit of individuals, this study places significant emphasis on delving into the phytochemical and ethnomedicinal attributes of A. augusta. Moreover, it seeks to bolster its findings with scientifically validated pharmacological investigations conducted through both in vivo and in vitro methodologies.

De novo drug design through artificial intelligence: an introduction

Developing new drugs is a complex and formidable challenge, intensified by rapidly evolving global health needs. De novo drug design is a promising strategy to accelerate and refine this process. The recent introduction of Generative Artificial Intelligence (AI) algorithms has brought new attention to the field and catalyzed a paradigm shift, allowing rapid and semi-automatic design and optimization of drug-like molecules. This review explores the impact of de novo drug design, highlighting both traditional methodologies and the recently introduced generative algorithms, as well as the promising development of Active Learning (AL). It places special emphasis on their application in oncological drug development, where the need for novel therapeutic agents is urgent. The potential integration of these AI technologies with established computational and experimental methods heralds a new era in the rapid development of innovative drugs. Despite the promising developments and notable successes, these technologies are not without limitations, which require careful consideration and further advancement. This review, intended for professionals across related disciplines, provides a comprehensive introduction to AI-driven de novo drug design of small organic molecules. It aims to offer a clear understanding of the current state and future prospects of these innovative techniques in drug discovery.

Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies.

Globally, malignancies cause one out of six mortalities, which is a serious health problem. Cancer therapy has always been challenging, apart from major advances in immunotherapies, stem cell transplantation, targeted therapies, hormonal therapies, precision medicine, and palliative care, and traditional therapies such as surgery, radiation therapy, and chemotherapy. Natural products are integral to the development of innovative anticancer drugs in cancer research, offering the scientific community the possibility of exploring novel natural compounds against cancers. The role of natural products like Vincristine and Vinblastine has been thoroughly implicated in the management of leukemia and Hodgkin's disease. The computational method is the initial key approach in drug discovery, among various approaches. This review investigates the synergy between natural products and computational techniques, and highlights their significance in the drug discovery process. The transition from computational to experimental validation has been highlighted through in vitro and in vivo studies, with examples such as betulinic acid and withaferin A. The path toward therapeutic applications have been demonstrated through clinical studies of compounds such as silvestrol and artemisinin, from preclinical investigations to clinical trials. This article also addresses the challenges and limitations in the development of natural products as potential anti-cancer drugs. Moreover, the integration of deep learning and artificial intelligence with traditional computational drug discovery methods may be useful for enhancing the anticancer potential of natural products.