p-TSA.H2O mediated one-pot, multi-component synthesis of isatin derived imidazoles as dual-purpose drugs against inflammation and cancer.

A novel one-pot multicomponent reaction was performed to synthesize different imidazole and benzotriazole (BTA) isatin-based medicinally important compounds using (p-TSA·H2O) as an economical and operative acid catalyst. The yield of the products was found to be up to a maximum of 92% when using this catalyst. Antioxidant, anti-breast cancer and anti-inflammatory activities of these 13 isatin-based derivatives (named as 5a-m) were assessed. The inhibitory effects of these compounds were tested in vitro against cyclooxygenase-2 (COX-2, an enzyme responsible for inflammation) and phosphoinositide-3 kinase (PI3K, a key enzyme in breast cancer). "Among the 13 isatin-based Imidazole derivatives, five compounds (5a, 5d, 5f, 5 k and 5l) were found to exhibit anti-inflammatory as well as anti-cancer activity, which was validated using HRBC stabilization assay (to show anti-inflammatory activity) and cytotoxicity in MCF-7 (breast cancer cell line) to provide proof for anti-cancer property of the compounds". The molecular interactions between the two enzymes were probed using molecular docking. Structure-Activity Relationship (SAR) and ADMET prediction results were also useful to screen the most effective imidazole derivatives and to establish them as putative COX-2 inhibitors/anti-inflammatory drugs. These selected compounds which showed appreciable activity against COX-2 and PI3K are promising drug candidates for the treatment of breast cancer and inflammation which is often associated with breast cancer pathophysiology.

N-substituted hydroxynaphthalene imino-oxindole derivatives as new class of PI3-kinase inhibitor and breast cancer drug: Molecular validation and structure-activity relationship studies.

N-substituted hydroxynaphthalene imino-oxindole derivatives (5a-g) were emerged as the inhibitors of the phosphoinositide 3-kinase (PI3K), which is a crucial regulator of apoptosis or programmed cell death. Electron donor-/acceptor-substituted indole-imine (5a-g) was achieved, and the structures were elucidated by FTIR, 1H NMR, 13C NMR and HRMS. Inhibition potency of PI3Ks was assessed by competitive ELISA. Subsequently, an anticancer activity against breast cancer (MCF-7) cell lines was evaluated. In both activities, compounds 5c, 5d and 5f showed most potent activities. Percentage inhibition for anticancer activity was 78.22 ± 1.02 (5c) and 78.98 ± 1.08 (5f), and the IC50 was 2.02 ± 0.92 µm (5c) and 1.98 ± 0.18 µm (5f). Compounds 5a and 5g were found inactive for both activities, and rest all showed a moderate activity. To get more insight into the binding mode and inhibitor binding affinity, 5a-g were docked into the active site of PI3Ks p110α (PDB ID: 2ENQ). Results suggested that the hydrophobic interactions in the binding pockets of PI3Ks conquered affinity of the most favourable binding ligands (5c and 5f: inhibitory constant (ki ) = 102.4 and 128.23 nm). The SAR studies demonstrate the efficiency of 5a-g as the PI3Ks precise inhibitors with the impending to treat various cancers.

Crico Arytenoid Joint Fixation in Diffuse Idiopathic Skeletal Hyperostosis (DISH): A Case Report.

Advanced form of diffuse idiopathic skeletal hyperostosis or Forestier's disease can induce dysphagia and significant airway symptoms such as hoarseness, snoring, dyspnoea on exertion and laryngeal stridor. We have discussed the diagnosis and management of an unusual case with respiratory distress due to left cricoarytenoid joint fixation and right vocal cord paresis in conjunction with skeletal pathology.

Evaluation of wound healing activity of some herbal formulations.

The wound healing activity of two herbal formulations (Himax ointment and lotion) containing Indradaru extract, i.e. Arjuna bark (Terminalia arjuna, Family-Combretaceae), extract was evaluated for its wound healing potential in two types of wound models in rats (i) excision wound model and (ii) incision wound model. Both the formulations responded significantly in both the wound models tested. The results were also comparable to that of the standard drug nitrofurazone used as a standard drug for comparison in this present investigation. The results were also comparable in terms of wound contracting ability, epithelization period, tensile strength and regeneration of tissues at the wound area. Thus, this investigation con fi rms the use of the Himax ointment and lotion containing Terminalia arjuna extract as a wound-healing agent as known from folklore medicine.