Quinic acid enhances kanamycin efficacy against methicillin-resistant Staphylococcus aureus biofilms.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) form biofilms that contribute to increased antimicrobial resistance, leading to treatment failure and/or relapse. It is, therefore, necessary to develop new antibiofilm strategies to eradicate MRSA biofilms related infections. This study was aimed to evaluate the effect of the combination of quinic acid and kanamycin against the preformed biofilms of methicillin-resistant Staphylococcus aureus.

Identification of new potential inhibitors of pteridine reductase-1 (PTR1) via biophysical and biochemical mechanism-based approaches: Step towards the treatment of Leishmaniasis.

Leishmaniasis is a parasitic disease, which spreads from the bite of an infected Phlebotomine fly to human hosts. The disease is characterized by a number of clinical manifestations, such as ulcerative lesions at the site of sandfly bite (cutaneous form), inflammation of mucosal membranes (mucosal leishmaniasis) or the deadly visceral form. This study was aimed to target pteridine reductase-1 (PTR1), a member of short chain dehydrogenases, which accounts for the reduction of conjugated and unconjugated pterins in Leishmania parasite.

Drug repurposing against fucosyltransferase-2 via docking, STD-NMR, and molecular dynamic simulation studies.

Aberrant fucosylation is the hallmark of malignant cell transformation, leading to many cellular events, such as uncontrolled cell proliferation, angiogenesis, tumor cell invasion, and metastasis. This increased fucosylation is caused due to the over-expression of fucosyltransferases (FUTs) that catalyzes the transfer of the fucose (Fuc) residue from GDP-fucose (donor substrate) to various oligosaccharides, glycoproteins, and glycolipids (acceptor substrates). Hence, fucosyltransferases (FUTs) are considered as validated target for the drug discovery against on cancers.

Synthesis, Aromatase Inhibition, Cytotoxicity and Molecular Docking Studies of New Fluorinated and Non-Fluorinated Thiourea Derivatives of Desloratadine.

Aromatase inhibitors are among the most effective treatment of the breast cancer. Aromatase catalyzes estrogen biosynthesis, which is a long-term cause of breast cancer. Current study describes the synthesis, purification of 26 new fluorinated and non-fluorinated thiourea derivatives of desloratadine (5), and their aromatase inhibition activity, cytotoxicity against cancer cell line (MDA-MB-231).

Identification of new leads against ubiquitin specific protease-7 (USP7): a step towards the potential treatment of cancers.

Ubiquitin-specific protease-7 (USP7) is an important drug target as it regulates multiple proteins and genes (such as MDM2 and p53) with roles in cancer progression. Its inhibition can hinder the function of oncogenes, increase tumor suppression, and enhance immune response. The current study was designed to express USP7 in a prokaryotic system, followed by screening of small molecules against it using biophysical methods, primarily STD-NMR technique.

Synthesis of isoniazid derivatives and evaluation of their α-chymotrypsin inhibitory effect through in silico guided in vitro studies.

Alpha-chymotrypsin is a serine protease. Its overexpression is responsible for several ailments, such as chronic obstructive pulmonary disease, autoimmune diseases, pancreatitis, and colon cancers. Therefore, the discovery of potent α-chymotrypsin inhibitors is essential for the treatment of the aforementioned ailments.

Bioassay-guided isolation of dehydrocostus lactone from as a leishmanicidal drug.

Several strains of parasite are involved in the occurrence of leishmaniasis infections, which makes its prevention and treatment very challenging. Currently, all forms of leishmaniasis are being treated with chemical drugs, which have limitations and adverse effects. Discovering antileishmanial agents from natural sources can lead to novel drugs against this dreadful disease.

Coumarin derivatives as new anti-biofilm agents against Staphylococcus aureus.

Staphylococcus aureus infections are the primary causes of morbidity, and mortality, particularly in immuno-compromised individuals. S. aureus associated infections are acquired from community, as well as hospital settings, and difficult to treat because of the emerging resistance against available antibiotics.

Structural basis for the binding of famotidine, cimetidine, guanidine, and pimagedine with serine protease.

Serine proteases are among the important groups of enzymes having significant roles in cell biology. Trypsin is a representative member of the serine superfamily of enzymes, produced by acinar cells of pancreas. It is a validated drug target for various ailments including pancreatitis and colorectal cancer.

Phytochemical investigation of Chrysanthellum americanum Vatke and its constituents- a targeted approach for the treatment of leishmaniasis.

The present study is focused on the isolation and identification of new therapeutic candidates from Chrysanthellum americanum Vatke., and their efficacy against pteridine reductase-1 (PTR1), a valid chemotherapeutic target in the Leishmania parasite. Henceforth, a new compound, chrysanamerine (1), along with 7 known compounds, polyacetylene 2, and flavonoids 3-8, were isolated from C.

Positive Regulation of Osteoblast Proliferation and Differentiation in MC3T3- E1 Cells by 7,3',4'-Trimethoxyflavone.

Objectives: Increasing ratio of bone fragility, and susceptibility to fractures constitutes a major health problem worldwide. Therefore, we aimed to identify new compounds with a potential to increase proliferation and differentiation of osteoblasts.

Methods: Cellular and molecular assays, such as ALP activity, alizarin staining, and flow cytometry were employed to check the effect of TMF on osteogenesis.

Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents.

We aim to develop new anti-leishmanial agents against and . A total of 23 thiourea derivatives of (±)-aminoglutethimide were synthesized and evaluated for activity against promastigotes of and . The -benzoyl analogue was found potent (IC = 12.

Neuro-regeneration or Repair: Cell Therapy of Neurological Disorders as A Way Forward.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression.

Synthesis of dimeric 1,2-benzothiazine 1,1-dioxide scaffolds: molecular structures, Hirshfeld surface analysis, DFT and enzyme inhibition studies.

1,2-Benzothiazines are bioactive compounds with diverse pharmacological properties. We report here the synthesis of a series of dimers containing 1,2-benzothiazine scaffolds as potential pharmacophores. The characterization of compounds was done using analytical techniques such as FT-IR, H NMR, and elemental analyses.

Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis and Cell Cycle Arrest.

Background: Drug repurposing in oncology promises benefits to many patients through its ability to provide novel, and fast-tracked treatments. Previous studies have demonstrated that depression may influence tumor progression. Anti-proliferative activity of certain antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), are reported in the literature.

Determination of hepatitis C virus subtype prevalent in Sindh, Pakistan: a phylogenetic analysis.

Hepatitis is a major public health issue, affecting 10-17 million people worldwide, with its prevalence continuously increasing. The Hepatitis C virus (HCV) is responsible for liver related diseases, which include liver cirrhosis, hepatocellular carcinoma, and chronic hepatitis. Pakistan is experiencing a serious rise in HCV cases.

Label free quantitative proteomic profiling of serum samples of intellectually disabled young patients revealed dysregulation of complement coagulation and cholesterol cascade systems.

Intellectual disability is a heterogeneous disorder, diagnosed using intelligence quotient (IQ) score criteria. Currently, no specific clinical test is available to diagnose the disease and its subgroups due to inadequate understanding of the pathophysiology. Therefore, current study was designed to explore the molecular mechanisms involved in disease perturbation, and to identify potential biomarkers for disease diagnosis and prognosis.

Identification, crystallization, and first X-ray structure analyses of phenyl boronic acid-based inhibitors of human carbonic anhydrase-II.

Human carbonic anhydrases (hCAs) play a central role in various physiological processes in the human body. HCAs catalyze the reversible hydration of CO into HCO, and hence maintains the fluid and pH balance. Overexpression of CA II is associated with diseases, such as glaucoma, and epilepsy.

Repurposing of US-FDA-approved drugs as negative modulators of ubiquitin specific protease-7 (USP7).

Ubiquitin-specific protease7 (USP7) regulates the stability of the p53 tumor suppressor protein and several other proteins critical for tumor cell survival. Aberrant expression of USP7 facilitates human malignancies by altering the activity of proto-oncogenes/proteins, and tumor suppressor genes. Therefore, USP7 is a validated anti-cancer drug target.

Cocrystals of a coumarin derivative: an efficient approach towards anti-leishmanial cocrystals against MIL-resistant Leishmania tropica.

Leishmaniasis is a neglected parasitic tropical disease with numerous clinical manifestations. One of the causative agents of cutaneous leishmaniasis (CL) is Leishmania tropica (L. tropica) known for causing ulcerative lesions on the skin.

Biochemical and Studies on Triazole Derivatives as Tyrosinase Inhibitors: Potential Treatment of Hyperpigmentation Related Skin Disorders.

Introduction: Tyrosinase is a versatile, glycosylated copper-containing oxidase enzyme that mainly catalyzes the biosynthesis of melanin in mammals. Its overexpression leads to the formation of excess melanin, resulting in hyperpigmentary skin disorders, such as dark spots, melasma, freckles, etc. Therefore, inhibition of tyrosinase is a therapeutic approach for the treatment of hyperpigmentation.

Yellow scorpion (Buthus sinidicus) venom peptides induce mitochondrial-mediated apoptosis in cervical, prostate and brain tumor cell lines.

Scorpion venoms are known to contain over 100,000 biologically active constituents. However, only a few of them have been studied. The major constituents of venom are proteins and peptides, which exhibit various biological and pharmacological properties, including anticancer activities.