Pharmacophoric screening of newly synthesized isoniazid derivatives and their antimycobacterial activity

Mycobacterium tuberculosis is clinically recognized as a causative agent of Tuberculosis. Keeping in view, this study was endeavored to screen our previously synthesized seventeen INH analogues for their antimycobacterial potential using proportion method. During this process, INH and all the seventeen compounds were examined at different concentrations of 0.05, 0.1 and 0.2microg/mL which were prepared using Lowenstein-Jensen [LJ] base. For drug susceptibility test, three Mycobacterial strains ATCC H37Rv, known INH-sensitive and INH-resistant strains were selected, sub-cultured on LJ Medium and serial diluted to achieve 1: 10, 1: 100, 1: 1000 and 1: 10000 from calibrated bacterial suspension Mcfarland No. 1. Dilutions of 1: 100 and 1: 10000 were added to drug free medium and 1: 100 bacterial suspension was added to each of the test concentrations and finally incubated for 4-6 weeks at 37 degree C. It was observed that only compounds II and XI were active against MTb. Compounds III, IX and X also showed activity but were less potent. Ligand Scout 3.02[il_10] was used to perform pharmacophore-based screening where important pharmacophoric features were identified in the structures of these compounds which could be related to their observed antimycobacterial activity

Synthesis, characterization and SAR of novel bezimidazole derivatives as nematicidal agents

Six novel analogues were prepared by reacting benzimidazole molecules [BM and CMB] propiophenone andbenzoyl chlorides respectively. The structures of newly synthesized compounds were determined with the help of spectroscopic techniques. The compounds were subjected to in-vitro screening for their activity against nematodes. It was observed that the benzimidazole [BM] derivatives possessed more nematicidal activity as compared to that of cyanomethyl-benzimidazole [CMB] for Meloidogyne incognita. Among them, the propiophenone substituted benzimidazole derivative B3 was found to be the most active compound and can be further studied as lead molecule for development of anthelmintic drugs

Cytotoxic and acute toxicity studies of isoniazid derivatives

Cancer is ultimately the result of cells that hysterically grow and do not die. Cells can experience uncontrolled growth if there are mutations to DNA, and therefore, alterations to the genes involved in cell division. Cancer occurs when a cell's gene mutations make the cell unable to correct DNA damage and is unable to destroy itself. There are over 100 different types of cancer each classified by the type of initially affected cell. Isoniazid, a well-known antitubercular agent has been reported to exhibit some cytotoxic activity. This finding prompt us to carry out this study where isoniazid and its sixteen derivatives were studied for any possible cytotoxic activity against Human astrocytoma SNB-19 cells, human Dukes' type C colorectal adenocarcinoma HCT-15 cells, human Dukes' type D colorectal adenocarcinoma COLO-205 cells, and human prostate adenocarcinoma [grade IV] PC-3 cells. Among the test compounds, SN-07 [a phenacyl derivative with para phenyl substitution] demonstrated slight cytotoxic effects on two types of human colorectal adenocarcinoma cells HCT-15 and COLO-205. Moreover, the acute toxicity of the compounds was also estimated in which some compounds were evaluated with more LD[50] values than isoniazid

Antimicrobial and antioxidant screening of N'-substituted sulphonyl and benzoyl derivatives of 4-Pyridine carboxylic acid hydrazide

In this research program, the antibacterial, antifungal and antioxidant activities of six N_-substituted sulfonyl and benzoyl derivatives of lead molecule PCH were reported. Out of these compounds, sulphonyl derivatives 2,3 and benzoyl derivative 5 showed moderate to good activity against different strains of gram-positive and gram-negative bacteria including B. cereus, B. subtilis, B. thruingiensis and S. pyogenes, S. fecalis and E. coli ATCC 8739. Moreover, upon antifungal screening, the compound, N?-[[2,4,6-trimethylbenzene] sulfonyl]pyridine-4-carbohydrazide possessed good antifungal activity against Candida species, a causative agent of systemic fungal infections. Antioxidant study demonstrated more than 50% inhibition in DPPH assay for sulphonyl derivative 2 indicating its potential as antioxidant while the other derivatives expressed low level of radical scavenging property

Antimalarial and insecticidal activities of newly synthesized derivatives of Benzimidazole

The bioactive benzimidazole and corresponding substituted phenacyl halides has been synthesized [11] new derivatives out of three compounds 8, 10 and 11 were found to inhibit the Plasmodium falciparum moderately after 72 hours of incubation hence acting as antimalarial agents. While these derivatives were exhibited negligible insecticidal activity too when analyzed by impregnated filter paper method

Determination of pKa values of new phenacyl-piperidine derivatives by potentiometric titration method in aqueous medium at room temperature [25 +/- 0.5[degree sign]C]

Dissociation constant [pKa] of ten novel phenacyl derivatives of piperidine were determined by potentiometric titration method in aqueous medium at room temperature [25 +/- 0.5oC]. The sample solutions were prepared in deionized water with ionic strength 0.01M and titrated with 0.1M NaOH solution. In addition, DELTAG values were also calculated. Different prediction software programs were used to calculate pKa values too and compared to the experimentally observed pKa values. The experimental and theoretical values were found in close agreement. The results obtained in this research would help to predict the good absorption of the studied compounds and can be selected as lead molecules for the synthesis of CNS active agents because of their lipophilic nature especially compound VII

Synthesis of novel derivatives of 4-Pyridine carboxylic acid hydrazide and their activity on central nervous system

Six novel derivatives [2-7] of 4-Pyridine carboxylic acid hydrazide [PCH] were synthesized by treating this lead molecule with substituted arylsulphonyl and benzoyl chlorides

The molecular structures of the newly derived products were characterized by the help of UV Visible, IR, FAB, 1HNMR spectroscopy and CHN analysis

During the preliminary pharmacological screening, it was observed that the synthesized compounds induced noticeable changes on motor activity of the animals

Interesting structure activity relationship was also observed among the synthesized molecules. Because of the interesting affect on motor activity, the newly synthesized derivatives can further be evaluated for their effects on CNS