ABSTRACT
The proteins encoded by the two major breast cancer genes (BRCA1 and BRCA2), ensure the stability of DNA and prevent uncontrolled cell growth; mutation of these genes is linked to the development of hereditary breast cancers. Exploration of human breast cancer inhibitors plays a vital role in the drug discovery process. In the current work, in silico studies were performed which involves a computational approach for the identification of active phytocompounds from the diverse set of medicinal plant products against the BRCA receptor. The in silico study through pharmacokinetics and pharmacodynamics properties shown promising outcomes for these phytocompounds data set as breast cancer inhibitors. It was observed that the compounds conformed to the Lipinski's rule of five and had good bioavailability. The drug-likeness model score and ADMET profile of the designed ligands also established their potential as a drug candidate. The docking study provided useful insights on potential target-lead interactions and indicated that the newly designed leads had a good binding affinity for BRCA targets. A pharmacophore model was built to explore the scaffolds for BRCA inhibitory activity. An effort is made to screen an inhibitor against BRCA targets by combining the use of ADMET, docking score, and pharmacophore model.Communicated by Ramaswamy H. Sarma.
Subject(s)
Breast Neoplasms , Molecular Dynamics Simulation , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Drug Discovery , Female , Humans , Ligands , Molecular Docking SimulationABSTRACT
Series of 2-[4-(2,4-dimethoxy-benzoyl)-phenoxy]-1-[4-(3-piperidin-4-yl-propyl)-piperidin-1-yl]-ethanone derivatives 9(a-d) and 10(a-d) were synthesized in good yield. The synthesized compounds were characterized by (1)H NMR, LC-MS, FTIR and elemental analysis. All the compounds were screened for in vivo wound-healing activity by incision and dead space wound models on Swiss albino rats. Significant wound healing was observed in 10b and 10d treated groups as also the epithelialization of the incision wound was faster with a high rate of wound contraction in these groups. The tensile strength of the incision wound was significantly increased in 10b and 10d compared to the Nitrofurazone, the standard skin ointment. In dead space wound model also the weight of the granulation was higher indicating increase in collagenation. The SAR correlation studies revealed that the thioamide functional linkage and electron withdrawing groups influence the wound-healing activity.
Subject(s)
Piperidines/chemical synthesis , Piperidines/pharmacology , Wound Healing/drug effects , Administration, Oral , Animals , Female , Male , Models, Biological , Piperidines/administration & dosage , Piperidines/chemistry , Rats , Rats, Wistar , Wounds and Injuries/pathology , Wounds and Injuries/physiopathologyABSTRACT
The use of nanostructured TiO(2) as mixed phase photocatalyst in the synthesis of 2H-pyrano/2H-thiopyrano [2,3-b]quinoline-2-carboxylic acid (2a/2b) is described. The binding modes of 2a/2b with ds DNA fragments d(CGCGAATTCGCG) were predicted by molecular docking studies. The lowest energy was found in the compound 2b with a binding energy of -7.44 Kcal/mol and inhibition constant of 5.39 x e(-6). The interaction study with CT DNA was carried out by absorption spectra, (K(b) constant obtained for 2a is 3.5x10(6) and for 2b it is 2.9x10(5)), viscosity and thermal denaturation methods. The in vitro antioxidant activities were evaluated. Finally, the results showed that the intercalated 2a/2b compounds are strong antioxidants and they protect oxidative DNA damage from harmful free radicals.
Subject(s)
Antioxidants/chemistry , DNA/chemistry , Microwaves , Models, Molecular , Quinolines/chemistry , Quinolines/chemical synthesis , Titanium/chemistry , Biphenyl Compounds/chemistry , Free Radical Scavengers/chemistry , Hydrogen Peroxide/chemistry , Hydroxyl Radical/chemistry , Molecular Structure , Nanostructures/chemistry , Nucleic Acid Denaturation/drug effects , Oxidation-Reduction , Picrates/chemistry , Quinolines/pharmacology , Spectrophotometry , Superoxides/chemistry , Transition Temperature/drug effects , ViscosityABSTRACT
We have characterized a new class of 2-mercapto/2-selenobenzo[h]quinoline-3-carbaldehyde (3/4). Antibacterial potential of these compounds against a wide range of gram-positive and gram-negative bacteria was studied. The selenium containing compound 4 showed significant inhibition zone on Staphylococcus aureus (22.76+/-0.14), Bacillus subtilis (20.63+/-0.24), and Streptococcus pyogenes (19.54+/-0.20) over sulfur containing compound 3. To validate the ethnotherapeutic claims of the synthetic compounds in skin diseases, wound healing activity was studied, besides antioxidant activity to understand the mechanism of wound healing. The interaction behavior of these compounds with DNA was investigated by absorption spectra (obtained K(b) constant for 3 is 2.7x10(5) and for 4 is 3.8x10(6)), viscosity, and thermal denaturation studies. Finally, the results show that the DNA intercalated 3/4 compounds are strong antioxidants; they show significant wound healing activity and protect oxidative DNA damage from harmful free radical reactions.
