Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters.

INTRODUCTION: Diabetes Mellitus is the metabolic disorder most prevalent globally, accounting for a substantial morbidity rate. The conventional drugs available for the management of diabetes are either expensive or lack the required efficacy. The purpose of this research is to isolate and characterize an active phytoconstituent from Coccinia grandis and assess its anti-diabetic properties. METHODS AND MATERIALS: Stems of Coccinia grandis are subjected to successive extraction and isolation. The isolated compound by column chromatography was characterized by FTIR (fourier-transform infrared), 1 H NMR (proton nuclear magnetic resonance), and Mass spectroscopy. The antidiabetic potential of the isolated compound was evaluated by in-vitro alpha-amylase inhibitory activity. Further, the compound was subjected to molecular docking studies to study its interaction with the human pancreatic alpha-amylase (Molegro Virtual Docker) as well to determine the pharmacokinetic and toxicity profile using computational techniques (OSIRIS property explorer, Swiss ADME, pkCSM, and PreADMET). RESULTS: The characterization of the compound suggests the structure to be 2,4-ditertiary butyl phenol. The in-vitro alpha-amylase inhibitory study indicated a concentration-dependent inhibition and the IC50 (median lethal dose) value of the isolated compound was found to be 64.36 µg/ml. The docking study with the A chain of receptor 5EMY yielded a favorable docking score of -81.48 Kcal mol-1, suggesting that the compound binds to the receptor with high affinity through electrostatic, hydrophobic, and hydrogen bonds. Furthermore, the silico ADME analysis of the compound revealed improved metabolism, a skin permeability of -3.87 cm/s, gastrointestinal absorption of 95.48 %, and a total clearance of 0.984 log ml min-1 kg-1. In silico toxicity analysis also predicted cutaneous irritations but no carcinogenicity, mutagenicity, or hepatotoxicity. CONCLUSION: The data suggested that the isolated compound (2, 4-tertiary butyl phenol) has the potential to inhibit the alpha-amylase activity and possess optimal ADME properties as well as tolerable side effects.

Novel thermo/pH sensitive nanogels composed from poly(N-vinylcaprolactam) for controlled release of an anticancer drug.

A series of novel nanogels (NGs) with both pH and thermoresponsive properties were synthesised by free radical emulsion polymerisation of N-vinyl caprolactam (VCL) and acrylamidoglycolic acid (AGA). 5-Flurouracil, an anti cancer drug, was successfully loaded into these nanogels via equilibrium swelling method. The encapsulation efficiency of 5-FU was found up to 61%. Here we present the novel potential drug delivery system showing both pH and temperature release of 5-FU. Fourier transforms infrared spectroscopy (FTIR), and differential scanning calorimetric (DSC) examined the structure and morphology of the NGs. Transmission electron microscopy (TEM) indicates the diameter of the NGs to be about 50 nm. The size distribution of NGs was investigated using dynamic light scattering (DLS), the average diameter and polydispersity is 57 nm and 0.194. Interestingly, the in vitro release studies of 5-FU demonstrated the dual nature (pH and temperature) of NGs. The cumulative release data were analysed using an emperical equation to compute the diffusion exponent (n); whose values suggest Fickian diffusion.

Synthesis and pharmacological evaluation of clubbed isopropylthiazole derived triazolothiadiazoles, triazolothiadiazines and mannich bases as potential antimicrobial and antitubercular agents.

A series of novel clubbed Isopropylthiazole derivatives triazolothiadiazines 2a-g, dihydro triazolothiadiazoles 3a-g, thioxotriazoles 4a-d, triazolothiadiazole 5, arylideneamino triazolethiones 7a-h and oxadiazolethiones 11a-b were synthesized and characterized by IR, (1)H NMR, (13)C NMR, elemental and mass spectral analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal and antitubercular activity against Mycobacterium tuberculosis H(37)Rv strain by broth dilution assay method. All the compounds exhibited moderate to significant antibacterial and antifungal activities. Results of the antitubercular screening against M. tuberculosis H(37)Rv showed compounds 7c and 7d exhibited good antitubercular activity (MIC 4 and 8 µg/mL) respectively, when compared with first line drug such as isoniazid (0.25 µg/mL).

Synthesis of some novel 2-substituted-5-[isopropylthiazole] clubbed 1,2,4-triazole and 1,3,4-oxadiazoles as potential antimicrobial and antitubercular agents.

In the present study a series of 2-substituted-5-[isopropylthiazole] clubbed 1,2,4-triazole and 1,3,4-oxadiazole derivatives have been synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. Synthesized compounds were evaluated for their preliminary cytotoxicity, antimicrobial and antitubercular activity against Mycobacterium tuberculosis H37Rv strain by broth dilution assay method. Antimycobacterial activity tested against M. tuberculosis indicated that compounds 4b and 6g exhibited twofold enhanced potency than parent compound 1 and the results indicate that some of them exhibited promising activities and they deserve more consideration as potential antitubercular agents. Compound 3c, 4b and 6c exhibited good or moderate antibacterial inhibition and compounds 3h and 7c showed excellent antifungal activity.

Synthesis of new 4-isopropylthiazole hydrazide analogs and some derived clubbed triazole, oxadiazole ring systems--a novel class of potential antibacterial, antifungal and antitubercular agents.

In the present study a series of 4-isopropylthiazole-2-carbohydrazide analogs, derived clubbed oxadiazole-thiazole and triazole-thiazole derivatives have been synthesized and characterized by IR, (1)H NMR, (13)C NMR, elemental and mass spectral analyses. The synthesized compounds were evaluated for their preliminary in vitro antibacterial, antifungal and antitubercular activity against Mycobacterium tuberculosis H(37)Rv strain by broth dilution assay method. The synthesized compounds 7a, 7b, 7d and 4 showed an antitubercular efficacy considerably greater than that of the parent 4-isopropyl-1,3-thiazole-2-carbohydrazide 1, suggesting that the substituted 4-isopropylthiazole-2-carbohydrazide moiety plays an important role in enhancing the antitubercular properties of this class of compounds. Compounds 2c, 3, 4, 6d, 7a and 7b exhibited good or moderate antibacterial and antifungal activity. Compounds 4 and 7b showed appreciable cytotoxicity at a concentration of 250muM.

Synthesis and anticonvulsant activity of some potent 5,6-bis aryl 1,2,4-triazines.

In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a~5f were synthesized by condensation of various benzils 4a~4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies. Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, (1)H NMR, (13)C NMR and mass spectroscopic data.