Morpholine Based Diazenyl Chalcones: Synthesis, Antimicrobial Screening and Cytotoxicity Study.

BACKGROUND: Microbial infections have been the major cause of morbidity and mortality for the centuries and continue to present the formidable challenge to the human health. Several studies have been performed to explore the antimicrobial potential of various synthesized chalcone derivatives. The morpholine derivatives are also gaining considerable importance due to diverse biological activities. Hybridization of morpholine and chalcone moiety together can be the useful approach for the development of new effective antimicrobial agents. METHODS: A new series of morpholine based heterocyclic diazenyl chalcones (MD1-MD21) was synthesized, characterized and evaluated for antimicrobial potential by tube dilution and agar diffusion methods. The most active derivatives were also evaluated for cytotoxicity towards mouse fibroblast cell line (L929) and the human lung cancer cell line (A549) and for haemolysis to check the toxicity on human red blood cells. RESULTS: MD-6 was found highly active against different microbial strains, particularly S. typhi, E. coli, A. niger and C. albicans having the MIC in the range of 1.95 µg/ml to 3.91 µg/ml. MD-9 and MD-21 were also found to have good antimicrobial activity. The most active diazenyl derivatives exhibited very low cytotoxicity towards L929 cell line (IC50 ranges from 360 µg/ml - 902.3 µg/ml) and A549 cell line (IC50 ranges from 35.42 µg/ml - 216.4 µg/ml) as compared to the standard drug 5-FU (IC50 ranges from 1 µg/ml - 2 µg/ml) against these cell lines. The active derivatives showed haemolysis of 10-15% up to 150 µg/ml concentration. CONCLUSION: MD-6, MD-9 and MD-21 were found to be most active antimicrobial agents. These derivatives demonstrated high safety profile by exhibiting very low cytotoxicity and also revealed their safety for human blood cells with haemolysis of 0.2-5.5% at their antimicrobial concentration.

A Review on Plant Antimicrobials of Past Decade.

As per WHO reports, about three-quarters (65-80%) of the world's population seek plants or plant-derived natural products for various diseases. The slow discovery of new synthetic molecules and rising resistance in microbes against existing ones has triggered an alarm for speeding up the development process for new molecules. Traditional system(s) of medicine and plant resources has been foresighted again by researchers to circumvent the situation. This review represents various plant genera which, either as a whole plant or their parts, have been reported possessing antimicrobial properties during the last decade. Before 2007, literature is already well cited in various books and reviews.

Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery.

New polymer therapeutics like polymer-drug conjugates (PDCs) are developing day by day. Heterocyclic drugs with excellent cytotoxic properties are available, but lack of their specificity makes them available to the normal cells also, which is the main cause of their toxicity. Drugs in the form of PDCs make delivery possible to the specific sites. Most of the PDCs are designed with the aim to either target and/or to get activated in specific cancer microenvironments. Therefore, the most exploited targets for cancer drug delivery are; cancer cell enzymes, heat shock protein 90 (HSP90), multi-drug resistance (MDR) proteins, angiogenesis, apoptosis and cell membrane receptors (e.g., folates, transferrin, etc.). In this review, we will summarize PDCs of heterocyclic drugs, like doxorubicin (DOX), daunorubicin, paclitaxel (PTX), docetaxel (DTX), cisplatin, camptothecin (CPT), geldanamycin (GDM), etc., and some of their analogs for efficient delivery of drugs to cancer cells.