Medicinal Chemistry

Ayurveda (Sanskrit word meaning “the scripture for longevity”) represents an ancient system of traditional medicine prevalent in India about 5000 years old. Rasayana concept of Ayurveda is believed to be useful to overcome challenging diseases to modern medicine i.e., regeneration of tissues after the disease condition like osteoarthritis, age related macular degeneration (AMD), Alzheimer's and Parkinsons disease, injuries, trauma, heart attack, stroke etc. Neurological and psychiatric disorders are generally associated with loss of memory, cognitive deficits, impaired mental function etc. The 'medhya rasayanas' are known to be beneficial to improve the intellectual e.g., mandukparni swaras, yashtimadhu churna with ksheer, guduchi swaras, and shankhapushpi kalka. Medhya Rasayana drugs are used for prevention and treatment of mental disorders of all the age groups. These drugs promote the Intellect (Dhi) Retention power (Dhriti), memory (Smriti). Mood disorders are known to be associated with considerable burden of disease, suicides, physical comorbidities, high economic costs, and poor quality of life. Therefore, it has become a major public health problem today. Unfortunately modern medicine based psychoactive drugs have met with limited success in treatment of various neurological and psychiatric disorders due to multi-factorial nature of these diseases. This review discusses about Medhya Rasayanas as a great player for prevention and management of age related cognitive decline.

This paper is a study on knowledge discovery for the prediction of characteristics of older patients with increased level of inflammation. The etiology of inflammation is thought to be multifactorial and associated with the development of chronic aging diseases. Chronic low grade inflammation, expressed by slightly elevated serumconcentrations of the inflammatory marker C-reactive protein (CRP), has been showed to be associated with increased frailty and overall and specific cardiovascular and noncardiovascular mortality. However, it has not been discovered before which conditions, taken all at once, are associated with elevated systems level of inflammation. To answer this question, we used the group of older primary health care attenders, burdened with multiple chronic conditions and described their health status by many aspects. The dataset was composed of 61 low-cost health parameters, many of which were data from patient health records. To predict the characteristics of patients with increased level of inflammation, we used a Linear Regression model and compared the results with some classfication algorithms. In this way, we selected 11 relevant predictors of inflammation and explained their meaning according to the existing knowledge. We could realise that many of them represent the components of the highly conserved functional network in which inflammation is the intermediate mechanism, linking these components together. These components include the metabolic, the neuroendocrineand the immune system, proposed as influencing each other during the development of age-related chronic diseases. We have also identified some new components, represented by the parameters indicating inflammation-mediated locomotor system disorders and the pituitary hormone prolactin serum concentration variations. This model, resulted from the knowledge discovery procedure, can be used to provide guidelines for further research on chronic low grade inflammation and for more practical purposes, to help physicians recognizing older persons who are at increased risk for frailty and death.

New N-Pyrazolylbenzamide derivatives which possess 2, 4-dinitrophenyl group were synthesized using 4, 4-dimethyl-3-oxo-pentanenitrile and 2, 4-dinitrophenyl hydrazine hydrochloride to afford an intermediate compound. The intermediate on auxiliary aroylation with substituted benzoyl chlorides in the presence of base yielded the subsequent N-Pyrazolylbenzamide derivatives (5a-l). The structures of newly synthesized compounds were elucidated by 1H NMR, FT IR and Mass spectral analysis. The anti-inflammatory activity of all newly synthesized was evaluated using carrageenan induced paw edema model and antimicrobial activity by serial dilution method. Six compounds (5d, 5f and 5h-k) showed consistently good anti-inflammatory activity in particular 4-trifluoromethyl-. N-[3'-t-butyl-1'-(2", 4"-dinitro)phenylpyrazol-5'-yl] benzamide (5h) was found to be the most effective among the other derivatives. The antimicrobial screening of all synthesized molecules showed that compounds 5f and 5h possess superior and encouraging activity against tested organisms

In this era of nanoscience, advances of nanotechnologyhave led to the creation of new generations of nanostructures, each characterized by their explorative utilization in various types of applications in biomedicine and bio-engineering. These applications are expected to significantly improve the diagnosis and therapeutic aspects of many diseases. The materials have been explored and reported as components of biosensors and as very efficient drug delivery platform. Though, few nano-materials have been reported to be used in clinical medicine, but not coherently effective. This could be because of nano-toxicity which is a potential limitation for its use in biological system. A brief description on the development of nanostructure for biomedical application over the years in terms of new materials and understanding of their interaction with the body, may lead to better biocompatible nanostructures.

Based on molecular docking analysis, nine alkyl 3,4-di-O-caffeoyl- quinates have been designed. Started from 3,4-di- O-caffeoylquinic acid (3,4-DCQA), all the compounds have been synthesized using thionylchloride as coupling reagent with yields of 56%-72%. By applying plaque reduction assay, the anti-respiratory syncytial virus (RSV) activities of all the compounds were evaluated. The IC50 values of all the derivatives were 2.9 to 7.8 times less than that of 3,4-DCQA itself. Isopropyl 3,4-Di-O-caffeoyl quinate (LS-4) was confirmed as the most active compound with IC50 value of 0.3 μM. It was indicated that hydrophobic groups with 2 to 4 carbon chain length were optimal for the enhancement of anti-RSV activity. Interestingly, all the derivatives showed greater cytotoxicity than 3,4-DCQA. Except LS-5, LS-6 and LS-9, all the derivatives have less toxicity than ribavirin. Furthermore, the stabilities of LS-4 in water, artificial gastric juice (AGJ), and artificial intestinal juice were evaluated, respectively. It was shown that LS-4 is stable in AGJ with the hydrolysis rate of 24.9% after 6 hours incubation at 37°C.

Despite recent therapeutic progress, cancer remains a major cause of death in industrialized countries. As a consequence, alternative treatments attract the attention of a growing number of patients. Among these therapies, the use of sodium bicarbonate to fight cancer has gained considerable interest. According to self-medication reports available on the internet, sodium bicarbonate is viewed by many patients as a simple, costless and efficient anti-cancer agent. Although no clinical study has demonstrated an anti-cancer activity of sodium bicarbonate up to date, emerging experimental reports indicate, that sodium bicarbonate may slow the progression of cancer. Here, we highlight the rationale to use sodium bicarbonate in cancer therapy and further enumerate experimental evidence for its anti-tumoral activity. Finally, we speculate about a future role of sodium bicarbonate in cancer therapy.