Pyrazolone incorporating bipyridyl metallointercalators as effective DNA, protein and lung cancer targets: Synthesis, characterization and in vitro biocidal evaluation.

Pyrazolone based metal complexes have strong bio-activity but the anti-cancer mechanism of these derivatives is not fully understood. In recent years, Cu(II) complexes have attracted the interest of researchers increasingly because of their high antitumor activities that are usually related to DNA binding. The reaction of three different derivatives (I) PPMP [3-methyl-1-phenyl-4-propionyl-1H-pyrazol-5(4H)-one], (II) TMCPMP [1-(3-chlorophenyl)-3-methyl-4-(4-methylbenzoyl)-1H-pyrazol-5(4H)-one] and (III) PPTPMP [3-methyl-4-propionyl-1-p-tolyl-1H-pyrazol-5(4H)-one] of 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and 2.2' bipyridyl along with Cu(NO3)2·3H2O under methanolic condition allowed us to isolate and characterize a series of new mixed ligand complexes [Cu(TMCPMP) (Bipy)NCS] (1) [Cu(PPMP) (Bipy)NCS] (2) and [Cu(PPTPMP) (Bipy)NCS] (3). All complexes are well characterized by elemental analysis, metal estimation, molar conductivity, FT-IR and UV-Vis spectroscopy. The molecular geometry of these complexes has been determined by single crystal X-ray study. The single-crystal X-ray structures of complexes 1 and 2 exhibit square pyramidal geometry, while complex 3 revealed slightly distorted square-pyramidal geometry. The DNA binding of these compounds with Calf-Thymus DNA (CT-DNA) has been explored by emission titration methods, which revealed that 1-3 could interact with CT-DNA through intercalation mode. The complexes also exhibited a strong binding with Bovine Serum Albumin (BSA) over the ligands. Complexes were evaluated for their in vitro cytotoxic activities against lung cancer cell lines (A549) as well as noncancerous rat cardiomyocytes (H9C2) cell lines, which showed that all three complexes exhibited substantial cytotoxic activity with minimum effect on noncancerous cells. Complex 1 with more hydrophobic environment exhibited relatively high cytotoxic activity towards A549 cells. In summary, this new series of compounds belongs to a class of copper-pyrazolonate complexes that target many biochemical sites and with potential anti-cancer activity. All these results collectively suggested that complexes could serve as promising pharmacologically active substance against lung cancer.

Effect of short photoperiod on organ growth kinetics and serum hormone profile in pullets of domestic fowl, Gallus gallus domesticus.

Effect of short photoperiod (SP; LD 6:18) treatment on serum hormone profile and growth rate of adrenal, thyroid, ovary, oviduct, liver and lymphoid organ was studied in rearing pullets (RIR breed) of 1 to day 90 old. Body weight and growth index of SP pullets were lesser as compared to pullets reared under LD 12:12. Except for ovary (recorded marginal increment), weights and growth indices of thyroid, adrenal and oviduct decreased under SP. Weight of liver and lymphoid organs was higher at 30 and 90 days, in SP pullets as compared to LD 12:12. Histometric data suggested that the transition from small to big follicles was slow in ovary of SP pullets, and also reduced follicular atresia was noted in SP pullets. Except for higher corticosterone level at 30 days and higher progesterone level at 30 and 60 days, relative levels of all the hormones at all other ages were lower in SP pullets. In general, the present observations suggested intraovarian changes in pullets exposed to SP.

Effect of dexamethasone and corticosterone on activity levels of ATPase, phosphomonoesterases and phosphodiesterase in liver, muscle and testis of post-hatched White Leghorn chicks.

Muscle ATPase activity did not show much change with any of the treatments, while hepatic total and Ca(2+)-Mg(2+)-ATPase activities were decreased with low dose of dexamethasone (DXM(L) and enzyme activity in general was increased with both high dose of DXM(H) and corticosterone. Total and Ca(2+)-Mg(2+)-ATPases were increased in testis of corticosterone treated chicks. Acid phosphatase activity of testis was increased with DXM(H) and decreased with DXM(L) while the enzyme activity in all the three tissues was increased with corticosterone. Muscle alkaline phosphatase activity was decreased with DXM treatments while that of testis was decreased with both DXM(H) and corticosterone treatments. Hepatic PDE activity was decreased with DXM and increased with corticosterone while muscle PDE activity was decreased under both DXM(H) and corticosterone treatments. The results suggest that both hypo. and hypercorticalism can induce tissue specific differential alterations in phosphomonoesterases, ATPases and PDE during early phases of post-natal development of chicks.