Thiosemicarbazones of p-aminobenzoic acid (PABA) were synthesized and tested for their antimicrobial and anticancer activity. Hydroxamate derivatives 4a-4l were found to have better antimicrobial and anticancer activity than their acid counterpart. Compound 4d was found to have good antimicrobial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Vibrio cholerae, and Bacillus subtilis with IC(50) value of about 1 µM. Compound 4f showed potent antifungal activity against Candida albicans (IC(50)  = 1.29 µM) and compound 4h showed potent anticancer activity (IC(50)  = 0.07 µM).

No abstract

No abstract

Curcumin, a natural diaryl heptanoid continues to be used as an alternative medicinal agent in many parts of South East Asia for treatment of many ailments. It can be usually obtained from substituted aryl aldehydes and acetylacetone and this route enables synthesis of a diverse set of curcumin analogues. Numerous analogues have been synthesized and tested by several researchers to investigate their activity against known biological targets and to improve upon the pharmacological and ADME profile by modifying substitutions on aromatic rings, β-diketone moiety and two flanking double bonds conjugated to the β-diketone moiety. Successful synthesis of such derivatives with modifications has resulted in the development of potential anticancer candidates that target various stages in cancer cell growth and development. Based on the evidences in modifications of these three functional elements, we have attempted to summarize the structure activity relationship of molecules which can be further utilized by researchers in medicinal chemistry in exploring the structure of curcumin.

Quinazoline derivatives are reported to have anti-inflammatory, analgesic, antibacterial, and anticancer activities. The incorporation of "OCH₂CONH₂" (oxymethylcarbamide) at 4th position of the quinazoline ring was found to influence the biological activities of the molecules. With this rationale, some new oxadiazolyl methyloxy quinazolines, pyrazolyl acetoxy methyl quinazolines, triazolylmethyloxy quinazolines were synthesized from anthranilic acid through quinazolyl oxyacetylhydrazide intermediates. All the compounds were characterized by IR, ¹H-NMR, EI-MS, and C, H, N analyses and evaluated for their antimicrobial activity. Docking studies on the DNA-gyrase enzyme (1KZN) show their role in the antimicrobial activity of the molecules and explain the higher potency of compounds 6a, 6b, 8a, 8b based on ReRanking scores and binding poses of the molecules.

The modern therapeutic approaches of antiepileptic agents against epileptic patients are showing many side effects, dose related effects and chronic toxicity. The aim of our present work is to evaluate anticonvulsant activity of isatin derivatives (Ia-Ij) to reduce the side-effects and increase the percentage protection from various stages of convulsions. No animals showed toxic effects even up to 2000mg/kg. It is evident that Ib, Ie, Ih, Ii and Ij showed anticonvulsant effect at the dose levels of 10 and 100mg/kg in MES test and except Ij all other derivatives exhibited antiepileptic effect at 10 and 100mg/kg in PTZ induced convulsions test. The isatin derivatives (Ib, Ie, Ih and Ii) which proved antiepileptic effect in both MES and PTZ induced convulsion models are selected and GABA levels in brain were estimated. They showed significant increase of GABA levels in brain.

DNA replication in eukaryotes is an intricate process, which is precisely synchronized by a set of regulatory proteins, and the replication fork emanates from discrete sites on chromatin called origins of replication (Oris). These spots are considered as the gateway to chromosomal replication and are stereotyped by sequence motifs. The cognate sequences are noticeable in a small group of entire origin regions or totally absent across different metazoans. Alternatively, the use of DNA secondary structural features can provide additional information compared to the primary sequence. In this article, we report the trends in DNA sequence-based structural properties of origin sequences in nine eukaryotic systems representing different families of life. Biologically relevant DNA secondary structural properties, namely, stability, propeller twist, flexibility, and minor groove shape were studied in the sequences flanking replication start sites. Results indicate that Oris in yeasts show lower stability, more rigidity, and narrow minor groove preferences compared to genomic sequences surrounding them. Yeast Oris also show preference for A-tracts and the promoter element TATA box in the vicinity of replication start sites. On the contrary, Drosophila melanogaster, humans, and Arabidopsis thaliana do not have such features in their Oris, and instead, they show high preponderance of G-rich sequence motifs such as putative G-quadruplexes or i-motifs and CpG islands. Our extensive study applies the DNA structural feature computation to delve into origins of replication across organisms ranging from yeasts to mammals and including a plant. Insights from this study would be significant in understanding origin architecture and help in designing new algorithms for predicting DNA trans-acting factor recognition events.

No abstract