Biomaterial Database

Structure-antitubercular activity relationship of phenothiazine-type calmodulin antagonists. 1995

P Ratnakar, and S P Rao, and P Sriramarao, and P S Murthy

Department of Biochemistry, University College of Medical Sciences, Shahdara, Delhi, India.

Six neuroleptic (antipsychotic) phenothiazine derivatives which are calmodulin antagonists were tested for their activity against Mycobacterium tuberculosis H37Rv in order to understand their structure-antitubercular activity relationship. Out of the six derivatives tested (trifluoperazine, chlorpromazine, triflupromazine, thioridazine, acetopromazine and fluphenazine), trifluoperazine appears to be a more potent antitubercular drug than others with a minimum inhibitory concentration (MIC) of 5 micrograms/ml. Chlorpromazine, triflupromazine and thioridazine are also active but less potent and have a higher MIC of 20 micrograms/ml. Acetopromazine and fluphenazine could not completely inhibit the growth even at a high concentration of 20 micrograms/ml. These results indicate that a methylpiperazinylpropyl group attached to the nitrogen (position 10) atom and trifluoromethyl group at the second carbon confer antitubercular activity to the phenothiazine molecule. It is suggested that trifluoperazine or one of its derivatives could be useful as one of the drugs in the multi-drug regimen for the treatment of tuberculosis with psychotic problems or vice versa.

UI	MeSH Term	Description	Entries
D008826	Microbial Sensitivity Tests	Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).	Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009169	Mycobacterium tuberculosis	A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.	Mycobacterium tuberculosis H37Rv
D010640	Phenothiazines	Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.
D002147	Calmodulin	A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.	Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D000995	Antitubercular Agents	Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.	Anti-Tuberculosis Agent,Anti-Tuberculosis Agents,Anti-Tuberculosis Drug,Anti-Tuberculosis Drugs,Antitubercular Agent,Antitubercular Drug,Tuberculostatic Agent,Tuberculostatic Agents,Antitubercular Drugs,Agent, Anti-Tuberculosis,Agent, Antitubercular,Agent, Tuberculostatic,Anti Tuberculosis Agent,Anti Tuberculosis Agents,Anti Tuberculosis Drug,Anti Tuberculosis Drugs,Drug, Anti-Tuberculosis,Drug, Antitubercular
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014150	Antipsychotic Agents	Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.	Antipsychotic,Antipsychotic Agent,Antipsychotic Drug,Antipsychotic Medication,Major Tranquilizer,Neuroleptic,Neuroleptic Agent,Neuroleptic Drug,Neuroleptics,Tranquilizing Agents, Major,Antipsychotic Drugs,Antipsychotic Effect,Antipsychotic Effects,Antipsychotics,Major Tranquilizers,Neuroleptic Agents,Neuroleptic Drugs,Tranquillizing Agents, Major,Agent, Antipsychotic,Agent, Neuroleptic,Drug, Antipsychotic,Drug, Neuroleptic,Effect, Antipsychotic,Major Tranquilizing Agents,Major Tranquillizing Agents,Medication, Antipsychotic,Tranquilizer, Major