Cytotoxicities of novel hydrazone compounds with pyrrolidine moiety: inhibition of mitochondrial respiration may be a possible mechanism of action for the cytotoxicity of new hydrazones

N,N'-Bis[1-aryl-3-pyrrolidine-1-yl)propylidene]hydrazine dihydrochlorides (R1-R7) were synthesized by the reaction of 2 mols of 1-aryl-3-(pyrrolidine-1-yl)-1-propanone hydrochlorides with 1 mol of hydrazine hydrate and reported for the first time with their detailed spectral analysis and cytotoxicities towards human hepatoma (Huh7) and breast cancer (T47D) cell lines. Compounds R2, R6, and R7 with the IC50 values of 5.16, 6.96, and 5.96 mu M, respectively, showed higher cytotoxic potency than the reference compound 5-FU with 7.0 mu M against Huh7 cell line. However, all compounds did not show better cytotoxic activities than 5-FU against T47D cell line at the conditions studied. The representative compound of series, R2, inhibited the mitochondrial respiration at 90, 165, and 265 mu M concentrations in a dose dependent manner in liver homogenates, suggesting that mitochondrial respiration may be one of the contributing factor to the cytotoxicity of the compounds synthesized. The compounds R2, R6, and R7 can be chosen as the leader compounds of this study for further studies

Cytotoxicity of Hydrazones of Morpholine Bearing Mannich Bases Towards Huh7 and T47D Cell Lines and Their Effects on Mitochondrial Respiration

N,N'-bis[1-(substitutedphenyl)-3-(morpholine-4-yl) propylidene] hydrazine dihydrochlorides, N1-N11 were designed and synthesized as cytotoxic agents. These compounds were synthesized by the reaction of 2 moles of 1-( substitutedphenyl)-3-(morpholine-4-yl)-1-propanone hydrochlorides with 1 mole of hydrazine hydrate. The compounds reported here are new, except N1 and N4. The cytotoxicity of the compounds was tested against human hepatoma (Huh7) and breast cancer (T47D) cell lines. 5-Fluorouracil (5-FU) was used as a reference compound. It was found that N3, which has 4-methoxy substituent on phenyl ring, was the most cytotoxic compound towards both cell lines. Its cytotoxicity was 5.6 times higher than 5-FU. Representative compounds N2 at 144, 264 and 424 mu M and N3 at 401 mu M concentrations significantly inhibited mitochondrial respiration in a dose dependent manner in liver homogenates. This suggests that the inhibition of mitochondrial respiration may be one of the contributing mechanisms to the cytotoxicity of the compounds. N3 may serve as a candidate compound for further studies

Crystal structure and theoretical study of (2E)-1-[4-hydroxy-3-(morpholin-4-ylmethyl)phenyl]-3-(thiophen-2-yl)prop-2-en-1-one

WOS: 000437492100018PubMed: 30002894In the title compound, C18H19NO3S, the morpholine ring adopts a chair conformation. The thiophene ring forms dihedral angles of 26.04 (9) and 74.07 (10)degrees with the benzene ring and the mean plane of the morpholine ring, respectively. The molecular conformation is stabilized by an O-H center dot center dot center dot N hydrogen bond. In the crystal, molecules are connected through C-H center dot center dot center dot O hydrogen bonds, forming wave-like layers parallel to the ab plane, which are further linked into a three-dimensional network by C-H center dot center dot center dot pi interactions involving the benzene rings and the methylene H atoms of the morpholine rings.Aksaray University, Science and Technology Application and Research Center, Aksaray, Turkey (State of Planning Organization) [2010K120480]The authors acknowledge the Aksaray University, Science and Technology Application and Research Center, Aksaray, Turkey, for the use of the Bruker SMART BREEZE CCD diffractometer (purchased under grant No. 2010K120480 of the State of Planning Organization

Crystal structure of 3-(thiophen-2-yl-carbonyl)-4-(thiophen-2-yl)-1-isopropyl-4-piperidinol, C17H21NO2S2

C17H21NO2S2, P (1) over bar (no. 2), a = 5.9254(2) angstrom, b = 8.9579(2) angstrom, c = 16.6787(4) angstrom, alpha = 92.570(1)degrees, beta = 99.158(2)degrees, gamma = 98.441(2)degrees, V = 862.4 angstrom(3), Z = 2, R-gt(F) = 0.0557, wR(ref)(F-2) = 0.1477, T = 293 K

Crystal structure of 4-[5-(4-fluorophenyl)-3-(4-hydroxyphenyl)-4,5-dihydropyrazol-1-yl] benzenesulfonamide, C21H18FN3O3S

C21H18FN3O3S, monoclinic, P 2(1) (no. 4), a = 11.6665(3) angstrom, b = 5.7483(2) angstrom, c = 14.7695(4) angstrom, alpha = 90 degrees, beta = 103.841(1)degrees, gamma=90 degrees, V = 961.72(5) angstrom(3), Z = 2, R-gt(F) = 0.0340, wR(ref)(F-2) = 0.0852, T = 296(2) K

Crystal structure of (E)-2-({4-hydroxy-5-methoxy3-[(4-methyl-1-piperazinyl) methyl] phenyl} methylidene)-1-indanone, C23H26N2O3

C23H26N2O3, triclinic, P (1) over bar (No. 2), a = 10.6646(19) angstrom, b = 10.7784(17) angstrom, c = 11.150(2) angstrom, alpha = 67.787(7)degrees, beta = 64.309(7)degrees, gamma = 64.271(7)degrees, V = 1011.6(3) angstrom(3), Z = 2, R-gt(F) = 0.0502, wR(ref)(F-2) = 0.1481, T = 293 K

Crystal structure of 3-(p-bromobenzoyl)-4-(p-bromophenyl)-1-isopropyl-4-piperidinol hydrochloride, C21H24Br2ClNO2

C21H24Br2ClNO2, monoclinic, P2(1)/n (no. 14), a = 10.3942(2) angstrom, b = 7.0862(2) angstrom, c = 29.3803(6) angstrom, beta = 93.508(2)degrees, V = 2160.0 angstrom(3), Z = 4, R-gt(F) = 0.0638, wR(ref)(F-2) = 0.0953, T = 294 K

Crystal structure of 1-{4-hydroxy-3-[(pyrrolidin-1-yl)methyl]phenyl}-3-phenylprop-2-en-1-one

WOS: 000375489100023PubMed: 27308021In the title compound, C20H21NO2, the pyrrolidine ring adopts an envelope conformation with the N atom at the flap position. The central benzene ring makes dihedral angles of 21.39 (10) and 80.10 (15)degrees with the phenyl ring and the mean plane of the pyrrolidine ring, respectively. The molecular conformation is stabilized by an intramolecular O-H center dot center dot center dot N hydrogen bond, which closes an S(6) ring. A weak C-H center dot center dot center dot pi interaction is observed in the crystal.State of Planning Organization [2010 K120480]The authors acknowledge the Aksaray University, Science and Technology Application and Research Center, Aksaray, Turkey, for the use of the Bruker SMART BREEZE CCD diffractometer (purchased under grant No. 2010 K120480 of the State of Planning Organization