Saikat Kumar Poddar

Synthesis, Characterization and Comparison of Local Analgesic, Anti-Inflammatory, Anti-Ulcerogenic Activity of Copper and Zinc Complexes of Indomethacin

BACKGROUND Non-steroidal anti-inflammatory drugs (NSAID) exert gastrointestinal upset by inhibiting mucosal cyclooxygenase (COX) activity and complexation technique with metals has been adopted to overcome this drawback. OBJECTIVE The study aimed to overcome the gastrointestinal side effects associated with indomethacin treatment by synthesizing copper (Cu) and zinc (Zn) complexes of indomethacin along with assessing potential pharmacological effects of these complexes. METHOD The characterization of synthesized complexes was done by FT-IR, XRD, UV-Vis, Atomic Absorption Spectroscopy (AAS) and Differential Scanning Calorimetry (DSC). Biological properties as local analgesic activity, anti-inflammatory activity and antiulcerogenic activity were evaluated following radiant heat tail flick, inhibition of rat hind paw edema and inhibition of NSAID induced gastroenteropathy method respectively. RESULTS 0.3 ml of indomethacin-copper complex demonstrated prominent analgesia at 25 µg/ml dose and 0.3 ml of indomethacin-zinc complex, after 30, 60 and 90 minutes of oral administration, shown significant local analgesia at 25, 50 and 100 µg/ml dose. In antiinflammatory activity assay, indomethacin-copper exhibited significant inhibition at 20 mg/kg dose after 2nd, 3rd and 4th hour of administration whereas indomethacin-zinc illustrated significant inhibition at 10 mg/kg dose after 2nd, 3rd and 4th hour of administration. Anti-ulcerogenic activity study of the complexes exhibited no macroscopic damage to the stomach and intestine, except minor microscopic damage. CONCLUSION In view of the results, the copper and zinc complexes of indomethacin may be used as better substitutes of the parent indomethacin owing to their minimal side effects with additional pharmacological effects.

Synthesis and characterization of cobalt and manganese complexes of indomethacin and comparative study of local analgesic, anti-inflammatory, and anti-ulcerogenic properties

The aim of the study was to synthesize cobalt and manganese complexes of indomethacin and their biological activity screening to uncover. The structures of metal complexes were elucidated by FT-IR, UV-Vis and atomic absorption spectroscopy, X-ray diffraction and calorimetric DSC. Heat radiant tail-flick test for local analgesic activity of cobalt complex of indomethacin in the doses of 50 and 100 μg/mL demonstrated potent local analgesic response. Manganese complex of indomethacin exhibited similar potent of activity at the dose of 100 μg/mL. Anti-inflammatory study of the indomethacin-manganese and indomethacin-cobalt complexes demonstrated their activity (paw edema inhibition of 71.67% at 20 mg/kg dose in the 1 h and 83.33% at 10 mg/kg dose in the 4 h) comparable with the standard diclofenac sodium. Gastrointestinal efficacy of cobalt and manganese complexes was close to that of indomethacin.

A review on Zika infection: From strain identification to Guillain-Barré syndrome complication

Abstract Zika infection, caused by Zika virus, is one of the life-threatening viral diseases of the 21st century. Though this virus came into our focus about 50 years ago, our understanding regarding this has not been improved till then. The probable reason lies within its characteristics of not showing any physical or physiological symptoms until the virus is spread to our next generation, new-born babies, who become mostly victims of microcephaly. The prime focus of this review was to demonstrate two focusing etiological features and complications related to Zika infection along with their findings. In the first study, the purpose was to isolate the virus strain and to find out the reason for not showing any physiological symptoms. The next study was about how Guillain-Barre syndrome can complicate the Zika infection in vector body. In short, a partial depiction of infection by Zika virus was tried to be focused.

Antibody-Drug Conjugates: A Review on the Epitome of Targeted Anti-Cancer Therapy

Cancer is one of the deadly diseases which is characterized by unchecked cell division or abnormal cell growth due to the incapability of cell cycle arrest. As the treatment for this is to kill the cancerous cells, the main challenge for scientists is to direct the cell killing to cancerous cells while leaving the normal cells unharmed. Antibody-Drug Conjugates (ADC) are one such targeted anti-cancer therapy. It is an effective drug delivery system that utilizes the targeting action of antibody along with cell death by potent cytotoxic agent, linked up with one another by a linker molecule and thus helps to reduce toxicity to non-target cells, ensure broad therapeutic window and overcome multi-drug resistance. Multiple parameters like total antibody (conjugated and unconjugated antibody), conjugated antibody, conjugated drug, unconjugated antibody and unconjugated (free) drug are needed to be analyzed to find out the behavior as well as safety and efficacy of ADCs. With 2 FDA approved drugs (Kadcylca and Adcetris) and more than 40 drugs undergoing clinical trial, this field has gained pace in recent years. Some challenges still persist in this field like reducing immunogenic response to antibodies, ensuring the ADC homogeneity and antibody-drug ratio, selection of appropriate targets, successful conjugation of drug to antibody, securing the stability of linkers in systemic circulation as well as improvement of oral bioavailability. With the advent of stable linkers, cytotoxic drugs having higher potency and better conjugation capability with the linker and antibodies having high specificity, these ADCs can overcome the limitations of cancer treatment. This review focuses on the criteria for proper construction of ADC, conjugation techniques, the target choices, the underlying mechanism of action and pharmacokinetic considerations associated with ADC.

Bioequivalence studies and pharmacokinetic properties of atorvastatin 40mg tablet in healthy bengali subjects

Abbreviations: tmax, time to reach the maximum concentration; Cmax, maximum plasma concentration; t1/2, half-life; AUC0-24, area under the plasma time curve up to last quantifiable time; AUC0-∞, area under the plasma time curve up to time infinity; kel, elimination rate constant; NCDs, non-communicable diseases; DGDA, directorate general of drug administration; TPR, total peripheral resistance

Comparative physicochemical, anti-inflammatory, and analgesic activity assay of synthesized chromium and nickel complexes of indomethacin

Abstract Objectives: Complexation of non-steroidal anti-inflammatory drugs (NSAIDs) with transition metals—chromium and nickel is a unique approach of masking the inherent side effect of gastrointestinal hemorrhage and ulceration of NSAID along with imparting beneficial pharmacological effects. Methods: Chromium and nickel complexes of indomethacin were synthesized followed by characterization of these complexes by FT-IR spectroscopy, UV–Visible spectroscopy, atomic absorption spectroscopy, calorimetric DSC analysis, and melting point analysis. For screening of biological activities to uncover potentially interesting pharmacological properties, the metal complexes were assayed for peripheral analgesic, central analgesic, and anti-inflammatory activity. Results: Nickel-indomethacin complex at dose of 20 mg/kg showed peripheral analgesia of 67.03% by inhibiting writhing and at its dose of 20 mg/kg showed potent central analgesic action at 60 min (92% elongation of tail flicking time). In anti-inflammatory study, nickel-indomethacin and chromium indomethacin complex at its 15 mg/kg dose in the 2 h showed inhibition of paw edema of 78.35 and 73.23%, respectively, which is comparable to the standard indomethacin. Conclusion: Based upon the results, it can be predicted that chromium and nickel complex of indomethacin may show promising pharmacological effects which can be revealed by extensive analysis using pharmacokinetic and pharmacodynamic test model.

Anti-inflammatory and Neuropharmacological activities of the seed extract of Setaria italica.

Setaria italica (Poaceae) has been used in folk medicine to treat inflammation, pain, arthralgia and many neurological disorders. The objective of the study is screening of ethanolic extract of Setaria italica seeds for possible anti-inflammatory and neuropharmacological activities in rats and mice respectively. Antiinflammatory activity was evaluated by carrageenan induced paw edema inhibition method while the neuropharmacological potential was evaluated by three separate methods: Hole-cross test, Open-field method and Phenobarbitone induced sleeping time test. The crude ethanolic extract of seeds of Setaria italica at 400 mg/kg body weight showed a strong anti-inflammatory activity with 20.16, 65.44, 65.5 and 71.15% inhibition of paw edema respectively after 1 st , 2 nd , 3 rd and 4 th hrs of carrageenan injection which is comparable to that of standard drug diclofenac sodium at 100 mg/kg body weight (% inhibition 92.3% at 4 th hour **P<0.001). In Hole-cross test, ethanolic extracts of Setaria italica at 400 mg/kg body weight dose have prominent CNS depressant activity which is comparable to standard Diazepam. In open field test, S. italica at 400 mg/kg body weight significantly suppressed the movements which is comparable to standard Diazepam. In Phenobarbitone induced test, Setaria italica did not show any significant CNS-depressant activity. The findings of the studies demonstrate anti-inflammatory and neuropharmacological properties of Setaria italica which could be therapeutic option against inflammation and neurological disorders.