Synthesis, Spectroscopic and Toxicity Studies of Titanocene Chelates of Isatin-3-Thiosemicarbazones

The reactions of bis(cyclopentadienyl)titanium(IV) dichloride with a new class of thiosemicarbazone (LH2), derived by condensing isatin with different N(4)-substituted thiosemicarbazides, have been studied and products of type [Cp2Ti(L)] have been isolated. On the basis of various physico-chemical and spectral studies, five coordinate structures have been assigned to these derivatives. Toxicity studies of titanocene complexes at tbur different concentrations have been carried out against snailLymnaea acuminata. The effect of most potent compounds on the activity of acetylcholinesterase enzyme, which inhibits the activity of enzyme, possibly by the formation of enzyme-inhibitor complex, was also studied.

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m-[o-(2-Chloro-5-Fluorosulfonylphenylureido)Phenoxybutoxy]Benzamidine: Affinity Labeling Reagent Which Can Identify Secondary Binding Sites of Coagulation Complement and Fibrinolytic Serine Proteases

10.1055/s-0038-1665767 ◽

1979 ◽

Author(s):

D Bing ◽

D Robison ◽

J Andrews ◽

R Laura

Keyword(s):

Binding Sites ◽

Serine Proteases ◽

Enzyme Inhibitor ◽

Molecular Model ◽

Factor Xa ◽

Affinity Labeling ◽

Catalytic Center ◽

Inhibitor Complex ◽

Polypeptide Chains ◽

Kinetics Of

We have determined that m-[o-(2-chloro-5-fluorosulfonylphenylureido)phenoxybutoxy]benza-midine [mCP(PBA)-F] is an affinity labeling reagent which labels both polypeptide chains of thrombin, factor Xa, complement component CIS and plasmin. As this means it is reacting outside of the catalytic center, we have called this reagent an exo-site affinity labeling reagent. Progressive irreversible inhibition of these enzymes by this reagent is rapid (k1st 2.5-4.6 x 10-3sec-1), the kinetics of inactivation are consistent with inhibition proceding via formation of a specific enzyme-inhibitor complex analogous to a Michaelis-Menton complex (KL - 115-26 μM), and diisopropylfluorophosphate or p-amidino-phenylmethanesulfonyfluoride Prevent labeling by [3H]mCP(PBA)-F. A molecular model of mCP(PBA)-F shows that the reactive SO2F group can be 17 A from the cationic amidine. The data are consistent with the hypothesis that both peptide chains are required for the specific proteolytic activity exhibited by these proteases and that the peptide chain which does not contain the active site serine is close to the catalytic center. (Supported by NIH and AHA grants

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Optimal Duration of the Preincubation Phase in Enzyme Inhibition Experiments

10.26434/chemrxiv.12016974.v1 ◽

2020 ◽

Author(s):

Petr Kuzmic

Keyword(s):

Enzyme Inhibition ◽

Dose Response ◽

Enzyme Inhibitor ◽

Single Point ◽

Association Rate ◽

Weakly Bound ◽

Inhibitor Complex ◽

Dissociation Equilibrium ◽

Optimal Duration ◽

Algebraic Formula

This report describes an algebraic formula to calculate the optimal duration of the pre-incubation phase in enzyme-inhibition experiments, based on the assumed range of expected values for the dissociation equilibrium constant of the enzyme–inhibitor complex and for the bimolecular association rate constant. Three typical experimental scenarios are treated, namely, (1) single-point primary screening at relatively high inhibitor concentrations; (2) dose-response secondary screening of relatively weakly bound inhibitors; (3) dose-response screening of tightly-bound inhibitors.

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A Very Short Hydrogen Bond Provides Only Moderate Stabilization of an Enzyme-Inhibitor Complex of Citrate Synthase

Biochemistry ◽

10.1021/bi00191a002 ◽

1994 ◽

Vol 33 (25) ◽

pp. 7753-7759 ◽

Cited By ~ 47

Author(s):

Ken C. Usher ◽

S. James Remington ◽

David P. Martin ◽

Dale G. Drueckhammer

Keyword(s):

Hydrogen Bond ◽

Citrate Synthase ◽

Enzyme Inhibitor ◽

Inhibitor Complex ◽

Short Hydrogen Bond

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Kinetic properties of the primary inhibitor of plasmin from human plasma

Biochemical Journal ◽

10.1042/bj1630389 ◽

1977 ◽

Vol 163 (2) ◽

pp. 389-391 ◽

Cited By ~ 74

Author(s):

U Christensen ◽

I Clemmensen

Keyword(s):

Human Plasma ◽

Enzyme Inhibitor ◽

Kinetic Properties ◽

Inhibitor Complex ◽

Rapid Formation ◽

Plasmin Inhibitor

The interaction of human plasmin with the newly discovered alpha2-plasmin inhibitor was investigated. It was found from rate measurements that the reaction involves the rapid formation of a first enzyme-inhibitor complex, followed by the slow irreversible transition to another complex. L-Lysine influences the first step, but not the second.

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Internalization of serratial protease into cells as an enzyme-inhibitor complex with alpha 2-macroglobulin and regeneration of protease activity and cytotoxicity.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)60908-1 ◽

1987 ◽

Vol 262 (23) ◽

pp. 10946-10950

Author(s):

H Maeda ◽

A Molla ◽

T Oda ◽

T Katsuki

Keyword(s):

Protease Activity ◽

Enzyme Inhibitor ◽

Inhibitor Complex

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Cube-Rhombellane Related Structures: A Drug Perspective

Molecules ◽

10.3390/molecules23102533 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2533 ◽

Cited By ~ 11

Author(s):

Mircea Vasile Diudea ◽

Claudiu Nicolae Lungu ◽

Csaba Levente Nagy

Keyword(s):

Single Point ◽

Molecular Graph ◽

Molecular Structures ◽

Combinatorial Synthesis ◽

Stability Evaluation ◽

New Class ◽

Physico Chemical ◽

Molecular Stability ◽

Internal Mobility ◽

Point Data

Rhombellanes represent a new class of structures, of which homeomorphs may be synthesized as real molecules. Cube-rhombellane is a double-shell structure, with vertices of degree 3 and 6, respectively. Several hypothetical structures/molecules were proposed and computed using molecular graph theory and coordination chemistry principles. Some geometries were optimized at the B3LYP/6-31G (d, p) level of theory, followed by harmonic vibrational frequency analysis at the same level of theory, single point data were collected in view of molecular stability evaluation. Some of the bioactive functionalized structures were also proposed and explored by molecular mechanics (MM)-based conformational analysis, to check their internal mobility. Drug-like properties of the proposed molecular structures were compared with some existing nano-molecules (fullerenes, nanotubes). ADME and other physico-chemical characteristics were computed using commercial software. Substructures of the proposed molecules, useful in a future synthesis, were provided by retro combinatorial synthesis (RECAP). Computational results obtained are promising regarding ADME properties, drug-likeness and nano-properties.

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