Synthesis of 1,3,5-trisubstituted pyrazolines as potential antimalarial and antimicrobial agents.

A series of novel 1,3,5-trisubstituted pyrazolines derivatives have been synthesized from chalcones and nicotinic acid hydrazide in two steps. In first step, chalcones were prepared by treatment of 4-hydroxy acetophenone with different substituted benzaldehyde by Claisen-Schimidt Condensation. In second step, various pyrazoline derivatives were prepared by reflux reaction of chalcones with nicotinic acid hydrazide in ethanolic solution. Compounds were confirmed by elemental analyses, IR, 1H NMR and 13C NMR spectral data and were evaluated for antimalarial and antibacterial activity. Compounds 5n (IC50=0.022µM for MRC-2 and IC50=0.192µM for RKL-9) displayed better antiplasmodial activity than the chloroquine (CQ) against chloroquine-sensitive (MRC-2) and chloroquine-resistant (RKL-9) P. falciparum strains. The in vitro cytotoxicity study conducted on the human HepG2 cell line (>30µM) and selectivity index (100-220) indicate that this series presents an interesting selective antiplasmodial profile. Further, in vitro heme crystallization inhibition assay showed compound 5e inhibited formation of ß-hematin more efficiently than CQ. In addition, antibacterial and antifungal evaluations were conducted, compounds 5c, 5i and 5j displayed better antibacterial activity against S. aureus, B. subtilis, E. coli and P. aeruginosa than ciproafloxacin. Antifungal activity of compound 5l against A. niger (MIC-3.25µg/ml) and C. albicans (MIC-6.5µg/ml) was found to be better than the standard drug fluconazole.

Nanoemulsion: A Novel Eon in Cancer Chemotherapy.

Cancer refers to an assemblage of lethal diseases characterized by abnormal growth of cells. The most celebrated adverse effects accredited to the cytotoxic class of anticancer agents are constructed owing to their inability to differentiate between the abnormally multiplying cancerous cell mass and the rapidly dividing healthy cells of the human body. Consequently, unknown targets chemotherapy for cancer play host to a multitude of adverse effects ranging from nausea, alopecia to torturous ages associated with the current treatment etiquette. Nano-pharmaceuticals constitute the advanced scale drug targeting technologies. Nanoemulsion is an important tool in the nano-technological arena designed for clinical and therapeutic application. Currently among different nano-carriers, nanoemulsions are extensively envisaged as efficient drug delivery systems for the targeted delivery of lipophilic cytotoxic antineoplastic agents. Beauties of nanoemulsion include optical clarity, biocompatibility, non-immunogenic, biodegradable, drug encapsulation, sustained and controlled release, nanometric size, large surface area, ease of preparation and thermodynamic stability. After excessive delving, the research fraternity has acknowledged nanoemulsions as proficient nanocarriers capable of effectively addressing the low bioavailability and noncompliance issues associated with the conventional anticancerous chemotherapeutic dosage forms. This review attempts to shed new light on the current status of nanoemulsion in the cancer therapeutics, and commercial field on the basis of morphology, formulation, characteristics and characterization parameters.

Comprehensive review on various strategies for antimalarial drug discovery.

The resistance of malaria parasites to existing drugs carries on growing and progressively limiting our ability to manage this severe disease and finally lead to a massive global health burden. Till now, malaria control has relied upon the traditional quinoline, antifolate and artemisinin compounds. Very few new antimalarials were developed in the past 50 years. Among recent approaches, identification of novel chemotherapeutic targets, exploration of natural products with medicinal significance, covalent bitherapy having a dual mode of action into a single hybrid molecule and malaria vaccine development are explored heavily. The proper execution of these approaches and proper investment from international agencies will accelerate the discovery of drugs that provide new hope for the control or eventual eradication of this global infectious disease. This review explores various strategies for assessment and development of new antimalarial drugs. Current status and scientific value of previous approaches are systematically reviewed and new approaches provide a pragmatic forecast for future developments are introduced as well.