Asian Journal of Research in Chemistry

Kaumil Navnitbhai Modi ¹, Palakben K. Parikh ¹, Hiren M. Marvaniya ¹, Dhrubo Jyoti Sen ¹

Affiliations
1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Gujarat Technological University, Arvind Baug, Mehsana-384001, Gujarat, IN

Abstract

9-methyl-1,5-diphenyl-3H,7H-pyrazolo-[1,2-a][1,2,4,6]-tetrazepine-3,7-dione ring system has been synthesised by the reaction between hydrazine and ethyl acetoacetate produced pyrazolone moiety which on benzoylation produced dibenzoyl derivative which on condensation with urea produced 9-methyl-1,5-diphenyl-3H,7H- pyrazolo-[1,2-a][1,2,4,6]-tetrazepine-3,7-dione ring which on alkaline oxidation with KMnO₄/KOH produced carboxylic moiety. Treatment with thionyl chloride of produced acid chloride derivative. This on condensation with Mannich base produced by benzaldehyde with urea/thiourea/guanidine produced the desired moiety.

The synthesised compounds were characterised by N% and spectral datas and antimicrobial and antifungal screening has been performed by zone of inhibition studies and MIC calculation with standard antibiotic/antifungal drug against (gram+ve) and (gram-ve) bacterial and fungal strains on agar media after 24 hours incubation at 37ۧC for antimicrobial activity and 24°C for antifungal activity. Gram positive: Staphylococcus aureus ATCC 9144, Bacillus subtilis ATCC 6633, Gram negative: Escherichia coli ATCC 25922, Fungal strain: Candida albicans ATCC 10231 It has been observed that the Compound-2 (X=S) showed maximum antibacterial activity against Escherichia coli, Compound-1 (X=O) and against Bacillus subtilis and Compound-1 (X=O) and against Staphylococcus aureus. Oxygen and Sulphur has two lone pairs whereas Nitrogen has one lone pair of electrons but the electronegativity of Oxygen (X=O; 3.5), electronegativity of Sulphur (X=S; 2.4) and electronegativity of Nitrogen (X=N+H; 3.1+2.2=5.3). MIC value of all the compounds have been found as 250μg as Minimum Inhibitory Concentration by serial dilution method and MIC of Cloxacillin is 250μg and for Fluconazole is 5.5μg.

Keywords

Pyrazolo-Tetrazepine, Antibacterial, Antifungal, Benzoylation.

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Ravi N. Patel ¹, Urviben Y. Patel ¹, Kiran M. Patel ¹, Jimit S. Patel ², Ankit D. Patel ¹, Dhrubo Jyoti Sen ¹

Affiliations
1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana- 384001, Gujarat, IN
2 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana- 384001, Gujarat, IN

Abstract

The inner eye of chemistry looks forward to the biology for getting the best output to design a potent drug molecule after crossing the iron gates of pharmacological as well as clinical trials. The basic scientific research in pharmacy is blooming in the impact of the compatibility of designed chemical molecule towards biological molecule. Latest technology in pharmaceutical science reflects the implementation of new methodologies to screen a new chemical entity in a biological system. The inner eye of chemistry looks forward to the biology for getting the best output to design a potent drug molecule after crossing the iron gates of pharmacological as well as clinical trials. The basic scientific research in pharmacy is blooming in the impact of the compatibility of designed chemical molecule towards biological molecule. Latest technology in pharmaceutical science reflects the implementation of new methodologies to screen a new chemical entity in a biological system. A representative problem in bioinformatics is the assembly of high-quality genome sequences from fragmentary "shotgun" DNA sequencing. Other common problems include the study of gene to perform expression profiling using data from microarrays or mass spectrometry. Framing the structural framework of a chemical molecule is first done by in-silico by computational chemistry and that is synthesized by in-situ method. This after synthesis the biological screening is done by both in-vitro and in-vivo studies to enlist as a potent moiety by QSAR. All these newer techniques possess a prefix “In” for in-vitro, in-vivo, in-situ and in-silico which are the In-ner eye of the members of pharmaceutical research.

Keywords

Optimization, Molecular Dynamics, Monte Carlo, Replica Exchange Method, Quantum Mechanics, In-Vitro, In-Vivo, In-Situ, In-Papyro and In-Silico.

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Ravi N. Patel ¹, Urviben Yashodharabhai Patel ¹, Ripal R. Chaudhari ¹, Dhrubo Jyoti Sen ¹

Affiliations
1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, IN

Abstract

Imidazole on reaction with chloroacetyl chloride afford 2-chloro-1-(1H-imidazole-1-yl)-ethanone, 1 which on treatment with hydrazine hydrate has yielded 2-hydrazinyl-1-(1H-imidazol-1-yl)-ethanone, 2. Condensation of 2 with various aromatic aldehydes afforded sustituted Schiff’s base of 2-hydrazinyl-1-(1H-imidazol-1-yl)-ethanone. The structures of all the products were characterized on the basis of their IR, Mass and ¹H-NMR spectroscopic data analysis. All the synthesised products were screened for their antibacterial activity against gram-positive and gram negative bacteria by cup-plate method.

Keywords

Synthesis, Imidazole, Aromatic Aldehydes, Schiff’s Bases, Antibacterial Activity.

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Priya R. Modiya ¹, Urviben Y. Patel ¹, Ravi N. Patel ¹, Dhrubo Jyoti Sen ¹

Affiliations
1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Gujarat Technological University, Arvind Baug, Mehsana-384001, Gujarat, IN

Abstract

Biological macromolecules are composed of one or more linear oligomers that fold into a functional form. The information that governs the final structure is encoded in the sequence of monomers and the precise functionality that they display, but accurate prediction of such structures remains a major challenge in structural biology. Recently, chemists have begun to develop small molecule systems that fold in a similar way and these may help to answer more complex questions or find applications in artificial molecular assemblies. Study of the properties of a family of oligoamides composed of alternating repeats of isophthalic acid and bisaniline building blocks have a rich supramolecular chemistry in non-polar solvents, forming macrocyclic receptors, catenanes, knots and double-stranded zipper complexes via a combination of amide–amide hydrogen bonds and aromatic interactions. Here the serendipitous discovery of a new member of the family that folds into a well-defined, compact, three-dimensional structure, governed by a combination of hydrogen bonding and aromatic interactions.

Keywords

Macromolecules, Oligomers, Biopolymers, Folder Polymers, Matrix Interactions.

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Bony R. Shah ¹, Dhrubo Jyoti Sen ¹, Rajesh Bahekar ²

Affiliations
1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, IN
2 Department of Medicinal Chemistry, Zydus Research Centre, Ahmedabad, Gujarat, IN

Abstract

Dipeptidyl Peptidase-IV (DPP IV) is a serine protease enzyme. It selectively cleaves first two amino acids (His- Ala/Gly) of 29 amino acids GLP-1 peptide and thereby makes it inactive. Thus, inhibition of DPP IV enzyme activity, using suitable DPP-IV inhibitor likely to increase the levels of endogenous intact and bioactive GLP-1 peptides, thereby, it acts as antidiabetic agents.

In this project, based upon SAR study of NVP-DPP728, we have designed new series of dipeptide based DPP-IV inhibitors, which mainly consist of five membere proline ring system, attached to sterically hindered aromatic acid, with suitable linker. Total 24 new compounds were prepared, using solid phase peptide synthesis (SPPS) approach and purified by prep-HPLC. All the test compounds were subjected for DPP IV inhibitory activity and also selectivity of test compounds was assessed against DPP8, DPP9 and QPP enzymes (in vitro). Most potent compounds from each series were subjected for in vivo antidiabetic activity. In vitro, compound IIIb and IIId was found to be most active (IC50 similar to sitagliptin) and selective. In vivo, compound IIIb showed significant blood glucose reduction @ 20 mg/kg dose (ip and oral route administration).

Keywords

DPP IV, Solid Phase Peptide Synthesis, Antidiabetic Activity.

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Sandip N. Badeliya ¹, Dhrubo Jyoti Sen ¹

Affiliations
1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, IN

Abstract

Receptor based drug design now plays a major role in the drug discovery. It may be applied to drug design depends highly on the availability of the receptor information. Systematic identification of protein-drug interaction networks is crucial to correlate complex modes of drug action to clinical indications and is applied to drug design when receptor structure is identified or characterized by high-resolution X-ray crystallography, NMR spectroscopy techniques or electron cryomicroscopy. The X-ray structures of a receptor and ligand-receptor complex provide greater and also some useful information about the binding cavity. Since binding sites of the receptor are very stereospecific so ligand or the drug molecule is modified in silico to achieve a better fit of the drug molecule to the binding site. This type of ligand modification is carried out by using sophisticated molecular modeling softwares. Especially by combinatorial chemistry drug synthesis is carried out in highly efficient manner and in larger quantities also. Trial and error approach of the ancient time is now totally changed. The aim is to achieve a better and novel drug that bind to its particular receptor.

Keywords

Receptor, Drug Design, De Novo Drug Design, Molecular Modeling, Computer Assisted Drug Design, Docking.

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Priya R. Modiya ¹, Palakben K. Parikh ¹, Deepa R. Parmar ¹, Dhrubo Jyoti Sen ¹, Vidhi R. Patel ¹

Affiliations
1 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Gujarat Technological University, Arvind Baug, Mehsana-384001, Gujarat, IN

Abstract

The study of chemical reactions on a very short time scale, often using pulsed lasers is femtochemistry. Etymology: From femtosecond + chemistry. Femto-(symbol f) is a prefix in the metric system denoting a factor of 10⁻¹⁵ or 0.000000000000001. Adopted by the 11th Conference Generale des Poids et Mesures, it was added in 1964 to the SI. It is derived from the Danish word femten, meaning "fifteen". Example of use: a proton has a diameter of about 1.6 to 1.7 femtometres. The femtometre shares the unit symbol (fm) with the older non-SI unit fermi, to which it is equivalent. The fermi, named in honour of Enrico Fermi, is often encountered in nuclear physics.

Keywords

Femto, Nano, Pump Pulse, Probe Plus.

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Nidhi J. Kapadiya ¹, Dhrubo Jyoti Sen ²

Affiliations
1 Pacific College of Pharmacy, Pacific Hills, Pratap Nager Extn., Airport Road, Debari, Udaipur-313003, Rajasthan, IN
2 Department of Pharmaceutical Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, IN

Abstract

Evaluation of structure activity relationship studies of synthesized diamides on CNS depression and sleeping time potentiation effect through intraperitoneally administration of various doses of test compounds in mg/kg dose in group of male albino mice using propylene glycol as an inert vehicle. The loss of righting reflex and regaining of it was noted for each compounds to determine the sleeping time, injecting drug (diazepam/pentobarbitone) solution to mice, compound+drug solution in the mice and only compound solution to another mice and observed it's sleeping time potentiation and by plotting the histogram sleeping time has been observed. It has been found that all the teat compounds do not have sleep inducing property. Sleeping time potentiation effect was studied for the teat compounds by using diazepam as benzodiazepine series and pentobarbitone as barbiturate series which show good sleep inducing property. The amide groups of compounds block the GABA receptor and chloride channel and shows longer duration of sleep inducing properrty due to the presence of two amide linkages on male albino mice. Maximum activity was shown by Compound-93 (b) due to the presence of two free -CONH2 linkages and also show more lipid solubility which block GABA receptor ling time produce their effect for longer period of time.
All the compounds exhibited significant CNS depression activity in combination with standard drug diazepam and pentobarbitone.

Keywords

Depression, Righting Reflex Method, Potentiation of Sleeping Time, Diazepam, Pentobarbitone.

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Yatri R. Shah ¹, Dhrubo Jyoti Sen ¹, C. N. Patel ¹

Affiliations
1 Department of Pharmaceutical and Medicinal Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya North Gujarat University, Arvind Baug, Mehsana-384001, Gujarat, IN

Abstract

CYP450 exists in prokaryotic and eukaryotic (plants, insects, fish and mammal, as well as microorganism).Different P450 enzymes can be found in almost any tissue:liver, kidney, lungs and even brain. It plays an important role in drugs metabolism and xenobiotics. Cytochrome P450 proteins in humans are drug metabolizing enzymes and enzymes that are used to make cholesterol, steroids and other important lipids such as prostacyclins and thromboxane-A2.Firstly CYP450 is discovered by R.T. Williams-in vivo, 1947. Brodie-in vitro, from late 40s till the 60s. Cytochrome P450 enzymes (hemoproteins) play an important role in the intra-cellular metabolism CYP enzymes have been identified from all lineages of life, including mammals, birds, fish, insects, worms, sea squirts, sea urchins, plants, fungi, slime molds, bacteria and archaea. More than 8100 distinct CYP sequences are known. CYP450 includes hydroxylation and various xenobiotic reactions. Clinical aspects of CYP450 include genetic polymorphism and drug drug interaction. Roche Amplichip test in very useful nowadays because many harmful reactions resulting from inappropriate dosing and treatment may be significantly reduced as clinicians can adjust the patient’s regimen accordingly. The AmpliChip Cytochrome P450 Genotyping System may help the doctor determine if a patient is at risk of adverse drug reactions or sub-optimal drug response. Thus it is very up growing technique to prevent adverse drug reactions.

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