br Acknowledgments br Introduction Heterocyclic chemistry ha
Introduction Heterocyclic chemistry has become one of the most important fields of research in pharmaceutical industry due to their many fold applications. Amongst all, heterocyclic ZD 9379 containing nitrogen and oxygen have shown most potent biological activities. It follows from the literature that depending on the type of substituent, the analogues of 1,2,4-triazole have a high potential for a wide range of biological activities such as antimicrobial,2, 3, 4 analgesic, anti-tumor, anti-inflammatory, anti-hypertensive, anti-cancer and antiviral activities. In a host of standard medicines 1,2,4-triazole moiety is present. 1,3,4-Oxadiazole is an essential core in heterocyclic chemistry and represents a key motif in medicinal chemistry due to their potential to exhibit bioactivities such as anti-HIV, analgesic,12, 13 anti-inflammatory,12, 13 anti-cancer,14, 15 antimalarial, antimicrobial and anti-tuberculosis. Medicines having 1,3,4-oxadiazole ring are plenty. Schiff bases also have gained importance in the field of medicine due to their wide spectrum of biological activities such as antimicrobial,17, 18, 19 anti-tubercular,20, 21, 22 anti-HIV, anti-cancer, anti-tumor, anti-inflammatory, analgesic and anticonvulsant.25, 26 Data from FTIR, NMR, mass and elemental analysis were used to characterize the compounds. The antibacterial and antifungal potency of these Schiff bases were investigated against certain standard strains. The activities of these compounds were compared with standard antibacterial and antifungal drugs. Molecular orbital calculations with DFT and PM6 have been done for the Schiff bases to correlate the antimicrobial activities with electronic parameters. The fission yeastSchizosaccharomyces pombe is an important model organism for the study of eukaryotic molecular and cellular biology. As eukaryotes, these yeasts can be used to study processes that are conserved from yeast to humans but absent from bacteria, such as organelle biogenesis and cytoskeletal organization or to study mechanisms such as transcription, translation and DNA replication, in which the eukaryotic components and processes are significantly different from those of their bacterial counterparts. Hence we studied the cytotoxic and genotoxic behaviors of compounds (S 1-SS 10) on S. pombe cells. Malaria remains a major cause of public health problem in about 95 countries mainly located in the tropical zone of the globe (notably Africa, South-East Asia and also Eastern Mediterranean region). This parasitic disease is still estimated to affect over 212 million people and accounted for 429,000 deaths in 2015. Five species of protozoan parasites belonging to the Plasmodium genus, namely falciparum, malariae, vivax, ovale and knowlesi cause malaria in human beings and Plasmodium falciparum is the most dangerous of these species.30, 31 The increasing prevalence of multiple drug resistant P. falciparum has significantly reduced the efficacy of the current anti-malarial drugs. Also, the resistance against P. falciparum is associated with mutations in the dihydrofolate reductase (DHFR) domain. Hence, DHFR enzyme has shown to be reliable and the best target to design new antimalarial drugs. Accordingly, we studied antimalarial activity against P. falciparum strain for the compounds (S 1-SS 10) and obtained IC50. Of these compounds, SS 2, SS 3, SS 4 and SS 9 were found to be significantly active. These compounds along with standard drugs (Chloroquine & Pyrimethamine) were docked with wild-type Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (pfdhfr-ts) complex (PDB ID: ) and their in vitro DHFR enzyme inhibition activity was also studied.
Materials and methods All starting materials and reagents were purchased from Sigma-Aldrich, Merck and Loba Chemie. Thin layer chromatography (TLC) was performed on silica gel G60 F254 (Merck) plates and eluted with the mobile phases n-hexane: ethyl acetate and methanol: chloroform (70:30% v/v). Melting points were recorded on automated melting point system and were uncorrected. Nicolet 6700 spectrophotometer (Thermo Scientific) was employed to record IR spectra using KBr pellet. NMR spectra were recorded on Bruker 400MHz using DMSO-d6 as solvent and TMS as an internal standard. Chemical shifts are reported in parts per million (δ in ppm). Mass spectra were recorded on Waters Micromass Q-Tof Micro. Elemental analysis was performed on the Thermo Scientific Flash 2000.