No abstract

The increasing level of antimicrobial resistance in pathogenic bacteria, together with the lack of new potential drug scaffolds in the pipeline, make the problem of infectious diseases a major public health concern. Thus, in this context, a novel series of 1,3,4-oxadiazole-substituted thiophenes (4 a-m) and 1,2,4-triazole (6 a-m) substituted thiophene derivatives were synthesized. Characterization of all the synthesized derivatives was done by various spectroscopic techniques such as 1 H NMR, 13 C NMR spectroscopy and mass spectrometry, and evaluated for antimicrobial activity against various pathological strains using broth dilution and disc diffusion method. In particular, compound 6 e and 4 e exhibited significant inhibitory potential with MIC ranging from 2-7 μg mL À 1 against S. aureus, B. subtilis, P. aeruginosa and E. coli. Additionally, compound 6 e was found to be highly potent against methicillin resistant S. aureus (MRSA; MIC = 2 μg mL À 1 ). Molecular docking studies were also performed to confer the possible mode of action and association studies indicate the binding of potent active compound with DHFR enzyme (K a = 2.10 × 10 3 M À 1 ). Further, the mechanism of action has also been explored by atomic force microscopy (AFM), which reveals the bacterial cell wall deformity and cell wall rupturing that may lead to bacteria cell death. Additionally, in silico ADME prediction study suggested the drug like properties of active compounds.

Polymer drug conjugates play an important role in the delivery of drugs. In the polymeric drug conjugates, the bioactive agent is combined covalently with polymer to achieve the efficient delivery of bioactive agents in the required or specific period of time along with the enhancement of permeability and retention time. A large number of biodegradable polymers have been widely used in the area of biomedical science. Among them, polyphosphazene, is a biodegradable polymer having versatile nature because of its two chlorine atoms attached on both sides of phosphorus atom of its polymeric backbone, it can be easily replaced by nucleophilic substitution reaction. A plenty of work has been explored for its biomedical applications such as tissue engineering, vaccine drug delivery, polyphosphazene- anticancer drug conjugates with doxorubicin, paclitaxel, platinum complexes, methotrexate and gemcitabine for the targeted drug delivery etc. This review is focused on the recent advances in the biomedical applications of polyphosphazene-drug conjugates.

In the present work, coumarin based pyrazolines (7a–g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential.