Exploring Potential Bioactive Components of Persea americana for the Treatment of Rheumatoid Arthritis through Network Pharmacology.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease character-ized by inflammation and joint destruction, leading to significant disability and reduced quality of life. Current treatment options for RA have limitations, highlighting the need for novel therapeu-tic approaches. In this study, we employed network pharmacology methods to identify potential bioactive compounds from Persea Americana (avocado) for the treatment of RA.

Exploring the Anticonvulsant Properties of a Celecoxib-Phospholipid Conjugate: Synthesis, Activation, and Evaluation of Cytotoxicity.

Background: Epilepsy poses a significant global health challenge, particularly in regions with limited financial resources hindering access to treatment. Recent research highlights neuroinflammation, particularly involving cyclooxygenase-2 (COX-2) pathways, as a promising avenue for epilepsy management.

Methods: This study aimed to develop a Cyclooxygenase-2 inhibitor with potential anticonvulsant properties.

"In-silico Design and Development of Novel Hydroxyurea Lipid Drug Conjugates for Breast Cancer Therapy Targeting PI3K/AKT/mTOR Pathway".

Hydroxyurea (HU) has shown promise in breast cancer treatment, but its hydrophilic nature limits its efficacy. Therefore, conjugating HU with lipids could increase its liphophilicity and improve its cellular uptake, leading to increased efficacy and reduced toxicity. The PI3K/Akt/mTOR pathway is an attractive therapeutic target in cancer not only because it is the second most frequently altered pathway after p53, but also because it serves as a convergence point for many stimuli.

Synthesis and screening of cyclic diketone indanedione derivatives as future scaffolds for neutrophil elastase inhibition.

Human neutrophil elastase (HNE) and proteinase 3 (Pr3) released from neutrophils at inflammatory sites are the major causes of pathogens in chronic obstructive pulmonary disease (COPD) and various lung tissue derangements, among which cystic fibrosis and blockade of airway passages are chronic. These proteolytic mediatory agents combined with induced oxidative reactions sustain pathogenicity. Cyclic diketone indane-1,3-dione derivatives were designed, and toxicity evaluation predictions were performed .

An In silico Investigation to Identify Promising Inhibitors for SARS-CoV-2 M Target.

Background: A limited number of small molecules against SARS-CoV-2 has been discovered since the epidemic commenced in November 2019. The conventional medicinal chemistry approach demands more than a decade of the year of laborious research and development and a substantial financial commitment, which is not achievable in the face of the current epidemic.

Objective: This study aims to discover and recognize the most effective and promising small molecules by interacting SARS-CoV-2 M target through computational screening of 39 phytochemicals from five different Ayurvedic medicinal plants.

Thioredoxin Interacting Protein Inhibitors in Diabetes Mellitus: A Critical Review.

Diabetes Mellitus (DM) is one of the highest contributors to global mortality, exceeding numbers of even the three major infectious diseases in the world, namely Tuberculosis, HIV AIDS, and Malaria. DM is characterised by increased serum levels of glucose caused by a loss of beta cells of the pancreatic islets, responsible for the secretion of insulin. Upon accumulation of data via a wide array of literature surveys, it has been found that Thioredoxin Interacting Protein (TXNIP) presents itself as a vital factor in controlling the production and loss of beta islet cells.

A novel family of small molecule HIF-1 alpha stabilizers for the treatment of diabetic wounds; an integrated , , and strategy.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a crucial regulator of wound healing, which includes epithelialization, angiogenesis, granulation, tissue development, and wound contraction. Even though diabetic wounds are hypoxic, HIF-1α levels are decreased during healing. Diabetic wound healing necessitates the modulation of hypoxia-induced responses by VHL-HIF-1α protein-protein inhibition.

Larvicidal and histopathological efficacy of cinnamic acid analogues: a novel strategy to reduce the dengue vector competence.

: A novel strategy such as conjugation of amino, Schiff's bases, and thiadiazole moieties to the cinnamic acid nucleus has been adopted in this study to discover new molecules that target the dengue envelope protein (DENVE). : Among the different domains of dengue virus envelope protein (PDB ID 1OKE), we have selected a ligand-binding domain for our structure-based drug design. The designed compounds have also been docked against DENVE protein.

Dengue Virus Entry/Fusion Inhibition By Small Bioactive Molecules: A Critical Review.

Many flaviviruses are remarkable human pathogens that can be transmitted by mosquitoes and ticks. Despite the availability of vaccines for viral infections such as yellow fever, Japanese encephalitis, and tick-borne encephalitis, flavivirus-like dengue is still a significant life-threatening illness worldwide. To date, there is no antiviral treatment for dengue therapy.

Effect of Anti-Retroviral Drug Impurity/Related Substances on the CCR5 and/or CXCR4 Receptors Binding Sites to Revise Resistance Mechanisms in the Clinical Implications Using Molecular Docking Studies.

Background: CCR5 and/or CXCR4 receptors on CD4+ T cell membranes are the active sites for HIV to bind. The different classes of drugs have a unique mechanism of action to cease the virus, but we are concentrating in the first-class i.e.

Distinct Modulation of Wild-Type and Selective Gene Mutated Vitamin D Receptor by Essential Polyunsaturated Fatty Acids.

Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor's (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness.

Withdrawal Notice: Design and Synthesis of a Novel Gabapentin- Phosphotidylcholine Conjugate for Targeting to Phospholipase A2 Enzyme through Nanostructured Lipid Carrier.

Unlabelled: The article for the journal Current Computer-Aided Drug Design has been removed by the Publisher due to acute language inconsistencies and grammatical errors. Bentham Science apologizes to the readers of the journal for any inconvenience this may cause. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.

Targeting a conserved pocket (n-octyl-β-D-glucoside) on the dengue virus envelope protein by small bioactive molecule inhibitors.

Dengue virus enters the cell by receptor-mediated endocytosis followed by a viral envelope (DENVE) protein-mediated membrane fusion. A small detergent molecule n-octyl-β-D-glucoside (βOG) occupies the hydrophobic pocket which is located in the hinge region plays a major role in the rearrangement. It has been reported that mutations occurred in this binding pocket lead to the alterations of pH threshold for fusion.

Dual Modulators of p53 and Cyclin D in ER Alpha Signaling by Albumin Nanovectors Bearing Zinc Chaperones for ER-positive Breast Cancer Therapy.

CDATA[The inherited mutations and underexpression of BRCA1 in sporadic breast cancers resulting in the loss or functional inactivation of BRCA1 may contribute to a high risk of breast cancer. Recent researchers have identified small molecules (BRCA1 mimetics) that fit into a BRCA1 binding pocket within Estrogen Receptor alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity, and overcome antiestrogen resistance. Studies indicate that most of the BRCA1 breast cancer cases are associated with p53 mutations.

Repurposing of Benzimidazole Scaffolds for HER2 Positive Breast Cancer Therapy: An Approach.

Background: A newer trend has been seen recently to reuse the conventional drugs with distinct indications for the newer applications to speed up the drug discovery and development based on earlier records and safety data. Most of the non-cancerous agents could afford a little or tolerable side effects in individuals. However, the repositioning of these non-cancerous agents for successful anticancer therapy is an outstanding strategy for future anti-cancer drug development.

Positive allosteric activation of glial EAAT-2 transporter protein: A novel strategy for Alzheimer's disease.

Excitatory amino acid transporter-2 (EAAT-2) protein localized in the membrane of glial cells are responsible for the clearance of glutamate in synapse and it plays a key role among the five glutamate transporters (EAATs) in regulating synaptic transmission and preventing excitotoxicity in neurons. EAAT-2 dysfunction has been associated with the neuropathology of Alzheimer's disease (AD). Impairment of EAAT-2 transporter function results excess accumulation of glutamate in synaptic cleft that acts on post-synaptic glutaminergic receptors excessively resulting in influx of Na and Ca ions into the neurons.

A New Class of Coumate Benzimidazole Hybrids as BRCA 1 Mimetics Through Unconventional Binding Mode; Synthesis and Preliminary Cytotoxicity Screening.

Background: It was found that breast cancer susceptibility protein 1 (BRCA 1) binds to estrogen receptor alpha (ERα) and inhibits its activity by direct interaction between domains within the amino terminus of BRCA 1 and the carboxy terminus of ER alpha.

Objectives: The present work focuses to identify a new class of BRCA 1 mimetics that work differently from conventional anti-estrogens.

Methods: A novel class of hybrids having coumate and benzimidazolone scaffolds were designed to mimic BRCA 1 protein, suppressing the tumor activity of breast cancer cells.

A new pyrimidine alkaloid from the roots of (L.) H.Ohashi.

(L.) H.Ohashi, also known as (Fabaceae) is the most important plant in the herbal remedies.

Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review.

Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors.

Isolation of methyl gamma linolenate from Spirulina platensis using flash chromatography and its apoptosis inducing effect.

Background: Isolation of methyl gamma linolenate from Spirulina platensis using flash chromatography and its apoptosis inducing effect against human lung carcinoma A- 549 cell lines.

Methods: Gamma linolenic acid is an important omega-6 polyunsaturated fatty acid (PUFA) of medicinal interest was isolated from microalgae Spirulina platensis using flash chromatography system (Isolera system) as its methyl ester. The isolated methyl gamma linolenate was characterized by IR, (1)H NMR, (13)C NMR and mass spectral analysis and the data were consistent with the structure.

Dual targeting DNA gyrase B (GyrB) and topoisomerse IV (ParE) inhibitors: A review.

GyrB and ParE are type IIA topoisomerases and found in most bacteria. Its function is vital for DNA replication, repair and decatenation. The highly conserved ATP-binding subunits of DNA GyrB and ParE are structurally related and have been recognized as prime candidates for the development of dual-targeting antibacterial agents with broad-spectrum potential.

Synthesis and characterization of some novel fatty acid analogues: a preliminary investigation on their activity against human lung carcinoma cell line.

Background: Preparation of some novel heterocyclic compounds with long alkyl and alkenyl chain of cytotoxic activity.

Methods: Gamma linolenic acid, a poly unsaturated fatty acid and stearic acid, a saturated fatty acid were isolated from the microalga Spirulina platensis. Some novel gamma linolenic acid and stearic acid analogues having 1,3,4-oxadiazole and 1,2,4-triazole were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis.

Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their antioxidant and anticancer activities as topoisomerase II inhibitors.

A series of 9-anilinoacridines substituted with oxazine derivatives were synthesized to evaluate their antioxidant and anticancer activity against Daltons Lymphoma Ascites (DLA) cell growth by in vitro method. It was revealed that these conjugates exhibited significant antioxidant and anticancer activity (inhibition of DLA cell proliferation). Among these agents, compounds 5a, 5h, 5i, 5j were the most cytotoxic with CTC(50) value of 140-250 μg/mL.

Synthesis, antidepressant and antimicrobial activities of some novel stearic acid analogues.

Stearic acid, a saturated fatty acid was isolated from the microalga Spirulina platensis. Some novel stearic acid analogues having 1,3,4-oxadiazole, 1,2,4-triazole and 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole are synthesized and characterized by IR, NMR and mass spectral analysis. All the synthesized compounds were screened for antimicrobial activity by using cup plate method.