Development Of New Drugs Research Articles

Breast cancer drugs: FDA approval, development time, efficacy, clinical benefits, innovation, trials, endpoints, quality of life, value, and price

ObjectiveThis study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval.MethodsWe identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000–2023). Data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) and tumor response’s relative risk (RR) alongside objective response rate (ORR) were meta-analyzed.ResultsThe median development time for breast cancer drugs was 7.8 years (95% CI 6.2–10.8). 26% of treatments were considered innovative (“first-in-indication”) with 88% acting via a targeted mechanism. 64% were small molecules, 19% antibodies, and 18% antibody-drug conjugates. 38% were approved for HR + and 31% for HER2 + breast cancer. 6 indications were for early and 36 for metastatic breast cancer. Indications utilized FDA’s special programs: orphan (2%), fast track (24%), accelerated approval (19%), priority review (74%), breakthrough therapy (44%). Approval was predominantly supported by phase 3 trials (88%) of randomized controlled design (66%), enrolling a median of 585 patients (IQR 417–752) at 181 centers (IQR 142–223) across 19 countries (IQR 17–20). New drugs’ HR were 0.78 for OS (95% CI 0.74–0.82) and 0.59 for PFS (95% CI 0.54–0.64) with a RR for tumor response of 1.61 (95% CI 1.46–1.76). Median improvements of OS were 2.8 months (IQR 1.8–5.8) and PFS were 4.4 months (IQR 2.2–7.1). In single-arm trials, the average ORR was 31% (95% CI 10–53). In meta-regressions, the correlation between OS/PFS was 0.34 (p = 0.031) and OS/response was 0.01 (p = 0.435). 60% of treatments had a ‘high-value’ ESMO-MCBS score with 14% demonstrating improvements in quality of life. The median price was $16,013 per month (95% CI 13,097–17,617). There was no association between prices and patient benefit. The median value per life year gained was $62,419 (IQR 25,840–86,062).ConclusionsOver the past two decades, the development of innovative and effective drugs transformed the treatment landscape for breast cancer patients. Yet, investigators and regulators must safeguard that highly-priced new drugs demonstrate improvements in patient-centered clinical endpoints: overall survival and quality of life.

Comparison of the difference in the anti-inflammatory activity of two different color types of Farfarae Flos based on in vitro, in vivo experiments and untargeted metabolomics.

Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored. This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms. Our findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos. This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos.

Neutralizing chimeric heavy-chain antibody targeting the L-HN domain of Clostridium botulinum neurotoxin type F.

Botulinum toxin (BoNT) from Clostridium botulinum is the most toxic biotoxin known and is also an important bioterrorism agent. After poisoning, the only effective treatment is injection of antitoxin. However, neutralizing nanoantibodies are safer and more effective, representing a promising therapeutic approach. Therefore, it is important to obtain effective neutralizing nanoantibodies. Hence, the present study aimed to construct a phage antibody library by immunizing a camel and screening specific clones that bind to the L-HN domain of BoNT/F and constructing chimeric heavy-chain antibodies by fusing them with a human Fc fragment. The antibodies' affinity and in vivo neutralizing activities were evaluated. The results showed that 2µg of F20 antibody could completely neutralize 20 × the median lethal dose (LD50) of BoNT/F in vitro. Injection of 5mg/kg F20 at 1h, 2h, 3h, and 4h into mice after BoNT/F challenge resulted in complete survival in vivo. Overall, the antibody might be a candidate for the development of new drugs to treat botulism.

Traditional Chinese Medicine Use in the Pathophysiological Processes of Migraine

Abstract Migraine is a highly prevalent neurological disorder and has been the second leading cause of disability worldwide for many years. The pathophysiology of migraines is complicated, and most available medications have unpleasant side effects. Therefore, it is essential to understand the mechanism of migraine to develop potential preventive and therapeutic agents. Studies have confirmed that traditional Chinese medicine (TCM) can alleviate migraine by reducing neuroinflammation, oxidative stress, and apoptosis and regulating neurotransmitters and vascular function. Starting from the pathophysiological process of migraine, this review summarizes the mechanisms by which TCM improves neurovascular function after migraine to provide clues and a reference for the clinical application of TCM in the prevention and treatment of migraine and guide further research and development of new drugs.

Some Aspects and Convergence of Human and Veterinary Drug Repositioning.

Drug innovation traditionally follows a de novo approach with new molecules through a complex preclinical and clinical pathway. In addition to this strategy, drug repositioning has also become an important complementary approach, which can be shorter, cheaper, and less risky. This review provides an overview of drug innovation in both human and veterinary medicine, with a focus on drug repositioning. The evolution of drug repositioning and the effectiveness of this approach are presented, including the growing role of data science and computational modeling methods in identifying drugs with potential for repositioning. Certain business aspects of drug innovation, especially the relevant factors of market exclusivity, are also discussed. Despite the promising potential of drug repositioning for innovation, it remains underutilized, especially in veterinary applications. To change this landscape for mutual benefits of human and veterinary drug innovation, further exploitation of the potency of drug repositioning is necessary through closer cooperation between all stakeholders, academia, industry, pharmaceutical authorities, and innovation policy makers, and the integration of human and veterinary repositioning into a unified innovation space. For this purpose, the establishment of the conceptually new "One Health Drug Repositioning Platform" is proposed. Oncology is one of the disease areas where this platform can significantly support the development of new drugs for human and dog (or other companion animals) anticancer therapies. As an example of the utilization of human and veterinary drugs for veterinary repositioning, the use of COX inhibitors to treat dog cancers is reviewed.

Antimalarial Mechanisms and Resistance Status of Artemisinin and Its Derivatives.

Artemisinin is an endoperoxide sesquiterpene lactone isolated from Artemisia annua and is often used to treat malaria. Artemisinin's peroxide bridge is the key structure behind its antimalarial action. Scientists have created dihydroartemisinin, artemether, artesunate, and other derivatives preserving artemisinin's peroxide bridge to increase its clinical utility value. Artemisinin compounds exhibit excellent efficacy, quick action, and minimal toxicity in malaria treatment and have greatly contributed to malaria control. With the wide and unreasonable application of artemisinin-based medicines, malaria parasites have developed artemisinin resistance, making malaria prevention and control increasingly challenging. Artemisinin-resistant Plasmodium strains have been found in many countries and regions. The mechanisms of antimalarials and artemisinin resistance are not well understood, making malaria prevention and control a serious challenge. Understanding the antimalarial and resistance mechanisms of artemisinin drugs helps develop novel antimalarials and guides the rational application of antimalarials to avoid the spread of resistance, which is conducive to malaria control and elimination efforts. This review will discuss the antimalarial mechanisms and resistance status of artemisinin and its derivatives, which will provide a reference for avoiding drug resistance and the research and development of new antimalarial drugs.

Antiplasmodial specialised compounds from the leaves of Guarea glomerulata Harms (Meliaceae)

To the best of our knowledge, this is the first chemical study of Guarea glomerulata that led to the isolation and characterisation of nine distinct compounds from its methanolic leaves extract including one new trinortriterpenoid glomerulatin along with eight known compounds amongst which five compounds namely azadirone, oleanolic acid, sericoside, cleomiscosin D and griffonin reported for the first time from the genus Guarea. All the isolated compounds have been evaluated in vitro for their antiplasmodial potency against the chloroquine-sensitive strain P. falciparum 3D7. The results showed that glomerulatin and azadirone were the most active compounds with IC50 values of 1.02 ± 0.2 μM and 1.48 ± 0.4 μM, respectively. This study enriches the chemistry of the genus Guarea and further supports the identification of Meliaceae plants as a good source of antiplasmodial candidates for the development of new potent drugs against malaria.

Innovative Bedaquiline-Based Delivery Systems for Multidrug-Resistant Tuberculosis Treatment

Abstract: The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) is one of the most challenging tasks in tuberculosis treatment. Conventional TB treatment regimens have proven ineffective in treating MDR-TB, thus demanding the development of new drugs followed by delivery systems. Bedaquiline, a novel anti-TB drug, has been reported to inhibit the ATP synthase required for the growth and replication of TB bacteria. Bedaquiline is able to target the persistent or latent form of TB, which remains difficult to treat with conventional drugs. This makes bedaquiline an important drug in the fight against MDR-TB. The drug has been approved by the US FDA as well as European Medicines Agency and is now widely used as part of combination therapy for the treatment of MDR-TB. Bedaquiline and its ad-vanced drug delivery system play a key role in tackling MDR-TB, providing a much-needed boost to control and eventually eliminate the disease. However, the cost of the drug remains a concern, and efforts are underway to make bedaquiline more accessible and affordable to patients in resource-limited settings. Nevertheless, the development of bedaquiline nanofor-mulations represents a significant step forward in the fight against TB and offers hope to millions of patients across the globe.

Thermoregulation Effects of Phoneutria nigriventer Isolated Toxins in Rats.

Body temperature is primarily regulated by the hypothalamus, ensuring proper metabolic function. Envenomation by Phoneutria nigriventer can cause symptoms such as hypothermia, hyperthermia, sweating, and shivering, all related to thermoregulation. This study aims to analyze and identify components of the venom that affect thermoregulation and to evaluate possible mechanisms. Rats were used for thermoregulation analysis, venom fractionation by gel filtration and reverse-phase chromatography (C18), and sequencing by Edman degradation. The venom exhibited hypothermic effects in rats, while its fractions demonstrated both hypothermic (pool II) and hyperthermic (pool III) effects. Further separations of the pools with C18 identified specific peaks responsible for these effects. However, as the peaks were further purified, their effects became less significant. Tests on U87 human glioblastoma cells showed no toxicity. Sequencing of the most active peaks revealed masses similar to those of the Tachykinin and Ctenotoxin families, both known to act on the nervous system. The study concludes that molecules derived from venom can act synergistically or antagonistically. Additionally, toxins that affect thermoregulation are poorly studied and require further characterization. These toxins could potentially serve as sources for the development of new thermoregulatory drugs.

The effect of the nisin-based pharmaceutical formulation used in the treatment plan for cows with subclinical mastitis on the milk microbiota

Due to the growing threat of antimicrobial resistance, the search and development of new drugs to treat infectious mammary gland diseases of high yielding cows is an urgent task. The paper presents data on the microbiota composition of milk from high yielding cows suffering from subclinical mastitis; 144 microbial isolates were recovered from 70 milk samples; with the highest number of Staphylococcus aureus and Streptococcus dysgalactiae detected (22.2 and 16.0%, respectively). The study showed that a significant number of Staphylococcus aureus isolates (53.1%) were resistant to I generation cephalosporins; 52.6% of the isolated Streptococcus dysgalactiae strains showed resistance to tetracyclines; 33.3% of Staphylococcus haemolyticus isolates were resistant to macrolides. 42.1; 35.3 and 62.5% of Enterococcus faecium, Aerococcus viridans and coliform bacteria isolates, respectively, were resistant to penicillins. 38.5% of Staphylococcus epidermidis isolates were found to be resistant to tetracyclines. Corynebacterium pseudotuberculosis isolates showed equal resistance to penicillin and tetracycline antimicrobials (20.0%). The research revealed presence of multi-drug resistant coliform bacteria, Streptococcus dysgalactiae, Aerococcus viridans, Staphylococcus aureus strains. Experiments to study the effect of the new nisin-based pharmaceutical formulation on microbiota of milk from cows with subclinical mastitis were carried out using 35 high yielding cows. A microbiological testing of cow milk on day 14 from the beginning of the treatment showed that the number of microbiota-free samples increased to 88.6%, while in 1.4% of cases Staphylococcus aureus isolates were recovered (103 CFU/mL). The titers of coliform and Staphylococcus aureus bacteria isolated in 1.4% (101 CFU/mL) and 2.7% (102 CFU/mL) of cases, respectively, were not etiologically significant.

The tumor suppressor Parkin exerts anticancer effects through regulating mitochondrial GAPDH activity.

Cancer cells preferentially utilize glycolysis for energy production, and GAPDH is a critical enzyme in glycolysis. Parkin is a tumor suppressor and a key protein involved in mitophagy regulation. However, the tumor suppression mechanism of Parkin has still not been elucidated. In this study, we identified mitochondrial GAPDH as a new substrate of the E3 ubiquitin ligase Parkin, which mediated GAPDH ubiquitination in human cervical cancer. The translocation of GAPDH into mitochondria was driven by the PINK1 kinase, and either PINK1 or GAPDH mutation prevented the accumulation of GAPDH in mitochondria. Parkin caused the ubiquitination of GAPDH at multiple sites (K186, K215, and K219) located within the enzyme-catalyzed binding domain of the GAPDH protein. GAPDH ubiquitination was required for mitophagy, and stimulation of mitophagy suppressed cervical cancer cell growth, indicating that mitophagy serves as a type of cell death. Mechanistically, PHB2 served as a key mediator in GAPDH ubiquitination-induced mitophagy through stabilizing PINK1 protein and GAPDH mutation resulted in the reduced distribution of PHB2 in mitophagic vacuole. In addition, ubiquitination of GAPDH decreased its phosphorylation level and enzyme activity and inhibited the glycolytic pathway in cervical cancer cells. The results of in vivo experiments also showed that the GAPDH mutation increased glycolysis in cervical cancer cells and accelerated tumorigenesis. Thus, we concluded that Parkin may exert its anticancer function by ubiquitinating GAPDH in mitochondria. Taken together, our study further clarified the molecular mechanism of tumor suppression by Parkin through the regulation of energy metabolism, which provides an experimental basis for the development of new drugs for the treatment of human cervical cancer.

Predicting of novel homoserine dehydrogenase inhibitors against Paracoccidioides brasiliensis: integrating in silico and in vitro approaches.

Aim: To search for potential inhibitors to homoserine dehydrogenase (HSD) in Paracoccidioides brasiliensis the causative agent of paracoccidioidomycosis, an infection with a high mortality rate in Brazil.Materials & methods: The enzyme was modeled and used in the virtual screening of the compounds. The library was first screened by the Autodock, in which 66 molecules were better ranked than substrate, and then, also evaluated by the Molegro and Gold programs.Results: The HS23 and HS87 molecules were selected in common by the three programs, and ADME/Tox evaluation indicates they are not toxic. The molecular dynamics of PbHSD bonded to ligands showed stable complexes until 50ns. To validate the results, compounds were purchased for assays of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), synergic profile with Amphotericin B (AmB) and cytotoxicity. The two molecules presented MIC of 32μg/ml and MFC of 64μg/ml against the P. brasiliensis (strain Pb18). They also showed synergistic activity with AmB and a lack of toxicity against Hela and Vero cell lines.Conclusion: These results suggest that the HS23 and HS87 are promising candidates as PbHSD inhibitors and may be used as hits for the development of new drugs against paracoccidioidomycosis.

In‐Vitro Antimicrobial, Antidiabetic and Anticancer Activities of Calyptocarpus Vialis Extract and its Integration with Computational Studies

AbstractCalyptocarpus vialis (C. vialis), a plant of Asteraceae family exhibits nutritional value, antioxidant properties and has potential for various other biomedical applications. The present study is focused to assess the antimicrobial, antidiabetic, and anticancer potential of C. vialis extract and its integration with computational studies. The antimicrobial activity is performed against the Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis) pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) bacteria and Saccharomyces cerevisiae (S. cerevisiae), Candida albicans (C. albicans) fungi using disc diffusion method. Maximum Zone of Inhibition (ZOI) of 37±3.2 and 35±2.9 mm is obtained for S. aureus and B. subtilis respectively, whereas ZOI of 39±2.8 mm is obtained against C. albicans at dose of 500 μg/mL. The extract shows strong α‐amylase inhibition activity with IC50 ~46.8±0.81 μg/mL inferring about its antidiabetic potential. Anticancer activity of C. vialis extract is checked against HCT‐116 and DU‐145 cell lines using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium‐bromide (MTT) assay, which shows excellent anticancer activity with IC50 value of 38.09±0.65 μg/ml and 36.34±1.05 μg/ml respectively. The obtained results are further verified using computational studies considering interaction among phytochemicals and selected targets. Extract is found potent for biological activities and promising candidate for development of new drugs.

Pharmacophore-based approach for the identification of potent inhibitors against LpxC Enzyme from Salmonella Typhi

Antimicrobial resistance (AMR) is currently a global health concern, mostly caused by microorganisms like bacteria, viruses, parasites, and fungi that acquire resistance to antimicrobial drugs. Salmonella is responsible for a variety of diseases but mainly cause typhoid. The primary concern is the rise in resistance in both non-typhoid and typhoid strains of this species. To address this issue, it is necessary to identify novel targets and strategies for the development of new antibacterial drugs. Lipid A, a strong bacterial endotoxin that modulates the immune system in human, is a key component of the virulence factor generated during the salmonella infection. Lipid A is synthesized in case of Gram-negative bacteria by cascade of nine enzyme pathway. The second step in case of Lipid A biosynthesis, catalysed by LpxC, a Zn+ dependent metallo-amidase considered as rate limiting step. In this manuscript we have used protein-ligand interaction fingerprint (PLIF)–derived pharmacophore models to screen small molecules (natural products library from Zinc database, Asinex database, Thiophene analogues) against Salmonella typhi LpxC (StLpxC). Further top hit molecules were subjected to MD-simulation and ADMET studies. We identified three optimal compounds, s1_dl_mseq2, s1_ll_mseq2, and s2_ll_mseq8, that exhibit strong binding affinity towards the LpxC active site.

The AMPK/cAMP Metabolic Signaling Axis as a Possible Therapeutic Target for Diabetes.

Diabetes is a complex disease, despite the availability of numerous treatments, its progression and complications can only be mitigated and managed to a certain extent. After the onset, diabetes cannot be reversed. Its global expansion makes it challenging for governments to control the considerable costs of treating people with diabetes. Many studies have been carried out by widely recognized pharmaceutical companies that are considering the development of new drugs for diabetic treatments. Diets, sedentary habits, and lifestyles that are currently prevalent have an enormous influence on the global spread of diabetes. The tools available to clinicians for therapy do not solve the problem. It is known that a patient, when diagnosed, would already have had diabetes for more than three years. Studies on diabetes signaling consider the effects of hyperglycemia but also highlight the roles of insulin receptor activation and resistance. Understanding the intricate signaling network and its interactions with hyperglycemiainduced pathways is crucial. In this context, the cyclic AMP/AMPK axis emerges as a promising therapeutic target for diabetes. However, there is a noticeable lack of literature exploring the metabolic network induced by hyperglycemia and its interconnected pathways. Therefore, investigating the cyclic cAMP/AMPK axis could provide valuable insights, given its complex connections with various metabolic pathways. This mini-review aims to delve into the metabolic signaling of the AMPK/cAMP axis in the context of diabetes, highlighting its metabolic interactions and potential implications.

Upfront or delayed surgery in resectable hepatoblastoma: analysis from the children’s hepatic tumors international collaboration database

In the treatment of resectable hepatoblastoma (HB), it has not been established whether upfront surgery (UF) at diagnosis or neoadjuvant chemotherapy and delayed surgery (DL) is preferred. We compared patients with localized HB who underwent either UF, or DL after neoadjuvant chemotherapy in the Children's Hepatic tumors International Collaboration (CHIC) database of 1605 cases enrolled in eight multicenter hepatoblastoma trials between 1988 and2010. Among the 512 resectable HB patients who had PRETEXT (PRETreament EXTent of disease) I or II unruptured tumors at diagnosis without extrahepatic invasion, distant metastases, or massive vascular invasion, 172 underwent UF and 340 underwent DL. The primary outcomes were event-free and overall survivals after start of treatment in these two groups. Survival analysis was performed using the Kaplan-Maier analysis with long-rank tests and multivariable Cox regression models. Complete resection rates were comparable (93.6% in UF and 89.7% in DL). The total cycles of chemotherapy of DL (median:6) were significantly more than those of UF (median:4) (P<0.01). The 5-year event-free survival (EFS) was 90.6% and 86.6% (P=0.89) in the UF and DL cohorts, respectively. The surgical complications, recurrence rates, and late complications were not significantly different between the cohorts but the EFS rates of DL patients with a low alpha-fetoprotein (AFP) level (100-999ng/mL) or older age at diagnosis (≥3 years old) were significantly worse than others. The outcomes, surgical resectability, and complications were not significantly different between the UF and DL groups. Eligible patients with a low AFP level (<1000ng/mL) or older age (≥3 years old) showed better outcomes in the UF group and might be considered for initial resection. European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission; Children's Oncology Group Cure Search grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research and Development; Japan Society for the Promotion of Science; and Swiss Cancer Research grant.

Exploring Novel Coumarin-Tethered Bis-Triazoles: Apoptosis Induction in Human Pancreatic Cancer Cells, Antimicrobial Effects, and Molecular modelling Investigations.

In the present study, we identified that two representative compounds (7c and 9f) of our newly synthesized coumarin-tagged bis-triazoles induced apoptosis in human pancreatic cells (PANC-1) by caspase 3/7mediated pathway. Both 7c and 9f (IC50 = 7.15 ± 1.19 and 6.09 ± 0.79 µM, respectively) were found to be ~100 times superior against PANC-1 as compared to the standard drug Gemcitabine (IC50 = >500 µM), without showing any toxicity to the normal pancreatic epithelial cells (H6C7). Molecular docking studies further endorsed them as potential pancreatic cancer therapeutics due to their strong hydrogen bonding interactions with the epidermal growth factor receptor (EGFR) enzyme, which is overexpressed in cancerous cells including pancreatic cancer. Additionally, these compounds also showed moderate inhibitory activity against a panel of microbial strains. Overall, our findings reveal that the coumarin hybrids 7c and 9f are viable chemotypes to be adopted as templates for the development of new anticancer drugs, particularly against pancreatic cancer.

Anthelmintic Activity of Alcoholic Leaf Extract of Tectona grandis

Background: Helminthiasis is a major concern in the livestock sector due to the immense afflictions in the production and economy of the farmer. Chemical anthelmintics are used to combat them and parasites are acquiring resistance against these drugs. Hence, the development of new drugs or alternatives is the need of the hour for combating such infestations. This study was undertaken to determine the effect of methanolic leaf extract of Tectona grandis on strongyles. Materials and Methods: The dried leaves of Tectona grandis were subjected to Soxhlet extraction using methanol, and the extract was tested for its anthelmintic activity in vitro using egg hatch assay and larval motility assay. A dose of 250, 125, 62.5, 31.25, 15.625, and 7.8125 mg/ mL was used for the study. Fresh strongyle ova were exposed to different concentrations of the extract and observed after 48 hours for the hatch. L3 larvae obtained from coproculture were subjected to treatment with extract at different concentrations, and mortality per unit time was calculated. Fourier transform infrared (FTIR) spectroscopic analysis and Gas chromatography-mass spectrometry (GC/MS) were performed to identify the chemical nature of the extract. Results: There was a dose-dependent inhibition of hatch and larval mortality with a maximum inhibition of hatch at 250 mg/mL. There was a cent percent hatch in control wells and no loss of progressive motility in the larval motility test. On exposure to the extract, the larvae progressively lost their motility, and finally, there were caesurae of movement which indicated their death. The extract at 250 mg/mL killed all the larvae by 30 min, whereas, at 31.25 mg/mL, the mortality was 66.6% after 2 hr. Conclusion: The results suggest that methanolic extract from Tectona grandis leaves has a promising anthelmintic property and further studies are required for the isolation of active molecules.

Antiviral Activity of Angelica Tenuissima Nakai against Influenza A Virus.

The influenza A virus poses a serious threat to human health and is an important global public health issue. The drugs currently used for treatment are becoming increasingly ineffective against influenza A viruses and require the development of new antiviral drugs. Angelica tenuissima Nakai (ATN), a traditional herbal medicine belonging to the Umbelliferae family, exhibits a broad range of pharmacological activities, including inflammation, headache, and cold symptoms. In the present study, based on target protein identification, functional enrichment analysis, and gene set comparisons, we first suggested that ATN has potential therapeutic effects against influenza A virus infection. Next, methylthiazol tetrazolium (MTT) and sulforhodamine B colorimetric (SRB) assay results revealed that ATN exhibited low cytotoxicity in Madin-Darby canine kidney (MDCK) cells. The antiviral properties of ATN were observed against H1N1 and H3N2 virus strains. Microscopy confirmed the increased survival rate of the host cells. Further time-of-addition experiments revealed that the addition of ATN before virus adsorption showed similar results to the whole period of treatment. The pre- and co-treated groups showed lower levels of viral RNA (M1 protein). The results of this study suggest that ATN exhibits antiviral properties against the influenza A virus. These therapeutic properties of ATN can serve as a theoretical basis for further research on the applicability of ATN in the development of antiviral agents.

Antitumor properties of griseofulvin and its toxicity.

Griseofulvin (GF), which is mainly extracted from Penicillium griseofulvum, is a heat-resistant, chlorine-containing non-polyene antifungal antibiotic. Previous research shows that GF has a variety of pharmacological effects, such as anti-inflammatory, antifungal, antiviral, and antitumor effects. In recent years, GF has received extensive attention for its antitumor effects as a natural compound, offering a low price, a wide range of uses, and other beneficial characteristics. However, no comprehensive review of GF pharmacological activity in tumors has been published so far. In order to fully elucidate the antitumor activities of GF, this review focuses on the antitumor potential and toxicity of GF and its derivatives, based on a literature search using PubMed, Web of Science, and other databases, to lay a good foundation for further research of GF and the development of new drugs for antitumor activities.