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

Prevalence and susceptibility patterns of bacteria causing respiratory tract infections in North Waziristan, Pakistan

Respiratory tract infections [RTIs] are the most common infectious diseases in humans and are the major cause of mortality and morbidity in Pakistan. These infections are the leading causes of consultations in primary care in Pakistan. Therefore, this study was aimed at determining bacterial pathogens of respiratory tract infections and the susceptibility patterns of bacterial isolates to antibiotics. The study was conducted between February, 2013 and March, 2014 in North Waziristan region of Pakistan. Sputum specimens were collected aseptically from 227 patients and cultured on the appropriate bacteriological media. Bacterial isolates were identified by biochemical tests and their antibiotics susceptibility patterns were determined by standard methods. Out of 227, various species of bacteria were isolated from 152 [75%] specimens. The prevalence of bacteria species isolated were as follows Pseudomonas aeruginosa [42.8%], Streptococcus pneumoniae [26.7%], Corynebacterium diphtheria [10.6%], Staphylococcus aureus [5.9%], Proteus vulgaris [4.6%], Micrococcus species [3.3%], Klebsiella pneumoniae [2.6%] and Bacillus species [2.6%]. The susceptibility patterns varied among bacterial species depending on the antibiotics. For the susceptibility test 11 commercially available antibiotics against bacterial isolates were used. The results revealed that generally the bacterial isolates were susceptible to gentamicin [80.9%], meropenem [75%], ceftazidime [62.5%], cefotaxime [57.9%] and ceftriazone [57.9%] and resistant to penicillin [84.9%] and doxycycline [78.9%]. The antibiotics gentamicin [100%] meropenem [100%], ceftriaxone [58.5%], ciprofloxacin [60%] trimethoprim [60%], ceftazidime [66.2%] and cefotaxime [64.6%] were observed effective against the P. aeruginosa isolates. The findings of our study provide significant information for empiric therapy of patients with RTIs in North Waziristan region of Pakistan

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

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

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