Molecular Diversity

Alzheimer's disease (AD) and osteoarthritis (OA) are both senile degenerative diseases. Clinical studies have found that OA patients have a significantly increased risk of AD in their later life. This study hypothesized that chronic aseptic inflammation might lead to AD in KOA patients. However, current research has not yet clarified the potential mechanism between AD and KOA. Therefore, this study intends to use KOA transcriptional profiling and single-cell sequencing analysis technology to explore the molecular mechanism of KOA affecting AD development, and screen potential molecular biomarkers and drugs for the prediction, diagnosis, and prognosis of AD in KOA patients...

Cimicifugae is a commonly used treatment for breast cancer, but the specific molecular mechanisms underlying its effectiveness remain unclear. In this research, we employ a combination of network pharmacology, molecular docking, and molecular dynamics simulations to uncover the most potent phytochemical within Cimicifugae rhizoma in order to delve into its interaction with the target protein in breast cancer treatment. We identified 18 active compounds and 89 associated targets, primarily associated to various biological processes such as lipid metabolism, the signaling pathway in diabetes, viral infections, and cancer-related pathways...

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75...

Cancer poses a significant global health challenge and significantly contributes to mortality. NEK7, related to the NIMA protein kinase family, plays a crucial role in spindle assembly and cell division. The dysregulation of NEK7 is closely linked to the onset and progression of various cancers, especially colon and breast cancer, making it a promising target for cancer therapy. Nevertheless, the shortage of high-quality NEK7 inhibitors highlights the need for new therapeutic strategies. In this study, we utilized a multidisciplinary approach, including virtual screening, molecular docking, pharmacokinetics, molecular dynamics simulations (MDs), and MM/PBSA calculations, to evaluate natural compounds as NEK7 inhibitors comprehensively...

Cluster of differentiation 147 (CD147) is an attractive target for anticancer therapy since it is pivotal in developing and progressing several of malignant tumors in the context of its high expression levels. Although anti-CD147 antibodies by different laboratories are designed for the Ig-like domains of CD147, there is a demand to provide priority among these anti-CD147 antibodies for developing of therapeutic anti-CD147 antibody before experimental validations. This study uses molecular docking and dynamic simulation techniques to compare the binding modes and affinities of nine antibody models against the Ig-like domains of CD147...

In this paper, a series of phenoxypyridine-containing chalcone derivatives (L1-L28) were designed and synthesized, characterized on NMR and HRMS. Ningnanmycin (NNM) was used as a control agent. The results of the antiviral activity testing showed that the curative activity EC50 values of L1 and L4 against TMV were 140.5 and 90.7 μg/mL, respectively, which were superior to that of NNM (148.3 μg/mL). The EC50 values of 154.1, 102.6 and 140.0 μg/mL for the anti-TMV protective activities of L1, L4 and L15 were superior to that of NNM (188...

This study aims to identify potential focal adhesion kinase (FAK) inhibitors through an integrated computational approach, combining mol2vec descriptor-based QSAR, molecular docking, ADMET study, and molecular dynamics simulation. A dataset of 437 compounds with known FAK inhibitory activities was used to develop QSAR models using machine learning algorithms combined with mol2vec descriptors. Subsequently, the most promising compounds were subjected to molecular docking against FAK to evaluate their binding affinities and key interactions...

Acute kidney injury (AKI) is a global health concern with high incidence and mortality, where diabetes further worsens the condition. The available treatment options are not uniformly effective against the complex pathogenesis of AKI-diabetes comorbidity. Hence, combination therapies based on the multicomponent, multitarget approach can tackle more than one pathomechanism and can aid in AKI-diabetes comorbidity management. This study aimed to investigate the therapeutic potential of esculetin and phloretin combination against AKI-diabetes comorbidity by network pharmacology followed by validation by molecular docking and dynamics...

Alzheimer's disease (AD) is a complex neurological disorder and no effective drug is available for its treatment. Numerous pathological conditions are believed to be responsible for the initiation and development of AD including c-Jun N-terminal kinases (JNKs). The JNKs are one of the enzymes from the mitogen-activated protein kinase (MAPK) family that controls the phosphorylation of various transcription factors on serine and threonine residues, and hold significant responsibilities in tasks like gene expression, cell proliferation, differentiation, and apoptosis...

Dengue virus, an arbovirus, leads to millions of infections every year ultimately leading to a high rate of mortality. Highly effective and specific therapeutic option is not available till date to combat viral infection. One of the first stages in the virus lifecycle encompasses the viral entry into the host cell which is mediated by the interaction between heparan sulphate and the Dengue virus envelope protein in turn leading to the interaction between the envelope protein receptor binding domain and host cell receptors...

Carbohydrates, one of the most abundant biomolecules found in nature, have been seen traditionally as a dietary component of foods. Recent findings, however, have unveiled their medicinal potential in the form of carbohydrates-derived drugs. Their remarkable structural diversity, high optical purity, bioavailability, low toxicity and the presence of multiple functional groups have positioned them as a valuable scaffold and an exciting frontier in contemporary therapeutics. At present, more than 170 carbohydrates-based therapeutics have been granted approval by varying regulatory agencies such as United States Food and Drug Administration (FDA), Japan Pharmaceuticals and Medical Devices Agency (PMDA), Chinese National Medical Products Administration (NMPA), and the European Medicines Agency (EMA)...

An important research topic is the discovery of multifunctional compounds targeting different disease-causing components. This research aimed to design and synthesize a series of 2-aryl-6-carboxamide benzoxazole derivatives that inhibit cholinesterases on both the peripheral anionic and catalytic anionic sides. Compounds (7-48) were prepared from 4-amino-3-hydroxybenzoic acid in three steps. The Ellman test, molecular docking with Maestro, and molecular dynamics simulation studies with Desmond were done (Schrodinger, 12...

Cancer, being the second leading cause of death globally. So, the development of effective anticancer treatments is crucial in the field of medicine. Anticancer peptides (ACPs) have shown promising therapeutic potential in cancer treatment compared to traditional methods. However, the process of identifying ACPs through experimental means is often time-intensive and expensive. To overcome this issue, we employed a machine learning-based approach for the first time to develop an anticancer model using small molecules...

One well-known multicomponent reaction that is helpful in the synthesis of dihydropyrimidinones (DHPMs), important molecules in organic synthesis and medicinal chemistry, is the Biginelli reaction. Because of their wide range of biological activities, DHPMs are regarded as essential chemicals. A great deal of research has been done in the last few decades to find ways to produce enantiomerically pure DHPMs because of their notable and focused target-oriented biological activities. In this reaction, numerous structural variants and catalysts have been employed in a range of solvents to yield an enormous number of Biginelli-type compounds...

In order to combat various infectious diseases, the utilization of host-directed therapies as an alternative to chemotherapy has gained a lot of attention in the recent past, since it bypasses the existing limitations of conventional therapies. The use of host epigenetic enzymes like histone lysine methyltransferases and lysine demethylases as potential drug targets has successfully been employed for controlling various inflammatory diseases like rheumatoid arthritis and acute leukemia. In our earlier study, we have already shown that the functional knockdown of KDM6B and ASH1L in the experimental model of visceral leishmaniasis has resulted in a significant reduction of organ parasite burden...

The mpox virus (MPXV), a member of the Poxviridae family, which recently appeared outside of the African continent has emerged as a global threat to public health. Given the scarcity of antiviral treatments for mpox disease, there is a pressing need to identify and develop new therapeutics. We investigated 5715 phytochemicals from 266 species available in IMMPAT database as potential inhibitors for six MPXV targets namely thymidylate kinase (A48R), DNA ligase (A50R), rifampicin resistance protein (D13L), palmytilated EEV membrane protein (F13L), viral core cysteine proteinase (I7L), and DNA polymerase (E9L) using molecular docking...

Cathepsin B is a cysteine protease lysosomal enzyme involved in several physiological functions. Overexpression of the enzyme enhances its proteolytic activity and causes the breakdown of amyloid precursor protein (APP) into neurotoxic amyloid β (Aβ), a characteristic hallmark of Alzheimer's disease (AD). Therefore, inhibition of the enzyme is a crucial therapeutic aspect for treating the disease. Combined structure and ligand-based drug design strategies were employed in the current study to identify the novel potential cathepsin B inhibitors...

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Telomeric regions contain Guanine-rich sequences arranged in a planar manner and connected by Hoogsteen hydrogen bonds that can fold into G-quadruplex (G4) DNA structures, and can be stabilized by monovalent metal cations. The presence of G4 DNA holds significance in cancer-related processes, especially due to their regulatory potential at transcriptional and translational levels of oncogene and tumor suppressor genes. The objective of this current research is to explore the evolving realm of FDA-approved protein kinase inhibitors, with a specific emphasis on their capacity to stabilize the G4 DNA structures formed at the human telomeric regions...

Halociline, a derivative of alkaloids, was isolated from the marine fungus Penicillium griseofulvum by our group. This remarkable compound exhibits promising antineoplastic activity, yet the precise molecular mechanisms underlying its anticancer properties remain enigmatic. To unravel these mechanisms, we employed an integrated approach of network pharmacology analysis, molecular docking simulations, and molecular dynamics simulations to explore halociline therapeutic targets for gastric cancer. The data from network pharmacology indicate that halociline targets MAPK1, MMP-9, and PIK3CA in gastric cancer cells, potentially mediated by diverse pathways including cancer, lipid metabolism, atherosclerosis, and EGFR tyrosine kinase inhibitor resistance...