Prabhakar Kumar Verma

A rational approach for the design and synthesis of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles as a new class of potential non-purine xanthine oxidase inhibitors.

Xanthine oxidase is a complex molybdoflavoprotein that catalyses the hydroxylation of xanthine to uric acid. Fifty three analogues of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles were rationally designed and synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. Six compounds 41, 42, 44, 46, 55 and 59 were found to be most active against XO with IC(50) ranging from 5.3 μM to 15.2 μM. The compound 59 emerged as the most potent XO inhibitor (IC(50)=5.3 μM). Some of the important interactions of 59 with the amino acid residues of active site of XO have been figured out by molecular modeling.

1,2,4-Triazole Derivatives as Potential Scaffold for Anticonvulsant Activity

The search for new anticonvulsant agent with more selectivity and lower toxicity continues to be an area of rigorous investigation in medicinal chemistry. Epilepsy is a chronic disorder of brain whose treatment consists of controlling seizures with antiepileptic drugs that very often related with side-effects which in rare circumstances can be potentially life-threatening. Triazolam and Alprazolam are established drugs used in epilepsy which have triazole moiety. The potency and broad spectrum of the pharmacological response of triazole moiety as anticonvulsant agent have attracted the attention of medicinal chemists to explore this framework for its potential. The literature shows that different substitution on triazole ring exhibit potent antiepileptic activity with no or lesser neurotoxicity. The present review is a sincere attempt to compile the reported potent triazole derivatives with significant anticonvulsant action.

Synthesis and therapeutic potential of quinoline derivatives

Quinolines are nitrogen-containing bicyclic compounds that are widely found throughout Nature in various forms. Quinoline derivatives are utilized in the areas of medicine, food, catalysts, dyes, materials, refineries, electronics, etc. The quinoline nucleus is present in numerous biological compounds, e.g., antimalarial, antimicrobial, antimycobacterial, antidepressant, anticonvulsant, antiviral, anticancer, antihypertensive, platelet-derived growth factor (PDGF) receptor tyrosine kinase (RTK) inhibitory, antiinflammatory, antioxidant, and anti-human immunodeficiency virus (HIV) agents. However, owing to the swift development of new molecules containing this nucleus, many research reports have been generated in a brief span of time. There therefore seems to be a requirement to collect recent information in order to understand the current status of the quinoline nucleus in medicinal chemistry research, focusing in particular on the numerous attempts to synthesize and investigate new structural prototypes with more effective antimalarial, antimicrobial, and anticancer activity.

Biological potential of pyrimidine derivatives in a new era

Pyrimidine and its derivatives play a wide role in drug discovery processes and have considerable chemical significance and biological activities. Pyrimidines are the building blocks of many natural compounds such as vitamins, liposacharides, and antibiotics. Pyrimidine is used as parent substance for the synthesis of a wide variety of heterocyclic compounds and raw material for drug synthesis and is also crucial in the theoretical development of heterocyclic chemistry and in organic synthesis. Pyrimidine derivatives are vital in several biological activities, i.e. antihypertensive, anticancer, antimicrobial, anti-inflammatory, and antioxidant activity. This creates interest among researchers who have synthesized a variety of pyrimidine derivatives.

Design, synthesis, and biological evaluation of thiourea and guanidine derivatives of pyrimidine-6-carboxylate

Two new series of methyl 7-methyl-5-(substituted-phenyl)-3,5-dihydro-2H—substituted [3,2-α]pyrimidine-6-carboxylate derivatives of thiourea and guanidine were synthesized. These compounds were characterized and evaluated for their antibacterial activity against Staphylococcus aureus, Bacillussubtilis, Escherichiacoli, and antifungal Aspergillus niger and Candida albicans and free radical scavenging activity using DPPH reagent method. Compound 7f was found to be the most active antibacterial and antifungal agent comparable to the standard drugs ciprofloxacin and fluconazole. Further, the compounds 5e, 7g, and 7h were also found to have significant antimicrobial activity. Compound 5a was found to be the most active antioxidant among all the targeted compounds, while compounds 5b, 5g, 7b, and 7f also had significant antioxidant activity compared to standard ascorbic acid.

Biological potential of thiazolidinedione derivatives of synthetic origin

Thiazolidinediones are sulfur containing pentacyclic compounds that are widely found throughout nature in various forms. Thiazolidinedione nucleus is present in numerous biological compounds, e.g., anti-malarial, antimicrobial, anti-mycobacterium, anticonvulsant, antiviral, anticancer, anti-inflammatory, antioxidant, anti-HIV (human immunodeficiency virus) and antitubercular agent. However, owing to the swift development of new molecules containing this nucleus, many research reports have been generated in a brief span of time. Therefore seems to be a requirement to collect recent information in order to understand the current status of the thiazolidinedione nucleus in medicinal chemistry research, focusing in particular on the numerous attempts to synthesize and investigate new structural prototypes with more effective antidiabetic, antimicrobial, antioxidant, anti-inflammatory, anticancer and antitubercular activity.

Synthesis and biological evaluation of thiazolo and imidazo N-(4-nitrophenyl)-7-methyl-5-aryl-pyrimidine-6 carboxamide derivatives

Two new series of thiazolo and imidazo N-(4-nitrophenyl)-7-methyl-5-aryl-pyrimidine-6 carboxamide derivatives were synthesized. All the synthesized compounds were evaluated for their antimicrobial activity against Gram-positive bacteria: Staphylococcusaureus MTCC 3160, Bacillus subtilis MTCC 441, Gram-negative bacterium: Escherichia coli MTCC 443 and antifungal activity against Candida albicans MTCC 227 and Aspergillusniger MTCC 281 and free radical scavenging activity. Compound 7e was found the most active antimicrobial comparable to standards taken. Compounds 7a, 7c, 9a, and 9d also showed significant antibacterial and antifungal activity. Further, compounds 7f, 9d, and 9h showed significant antioxidant activity with IC50 comparable with the standard compound. The synthesized compounds were confirmed for their structure by means of various spectrometric techniques like IR, 1H NMR, mass, and elemental analysis.

Insignificant anticancer activity of novel substituted pyrimidine derivatives

Background: Pyrimidine and fused pyrimidine derivatives play an important role in therapeutic strategies. It is known to be most prominent structures found in nucleic acid, including uracil, thymine, cytosine, adenine, and guanine, which are fundamental building blocks for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Materials and Methods: A series of 3-[2-amino-6-(substituted)-pyrimidin-4-yl]-6-(substituted)-2H-chromen-2-one derivatives were prepared by reacting salicylaldehyde with ethylacetoacetate in the presence of piperidine by Knoevenagel reaction as a starting material. The chemical structures were confirmed by means of FTIR (Fourier Transform InfraRed Spectrophotometer-8400S), 1H NMR, and elemental analysis. The data of these synthesized compounds were submitted to National Institute of Health, USA, under the drug discovery program of NCI (National Cancer Institute) and screened for anticancer activity at a single high dose (10−5 M) in full NCI 60 cell lines. Results: Unfortunately, the selected compounds have not shown any potent significant anticancer activity in the NCI 60 cell line screening. Conclusion: The compound (T2) found to be most efficient anticancer activity with selective influence on breast cancer cell lines, especially on MCF7 cell line with a growth percentage of 33.63.

Pyrimidine containing furanose derivative having antifungal, antioxidant, and anticancer activity

Background A series of 6-(substituted aldehyde)-3,4-dihydro-1-(tetrahydro-3,4-dihydroxy-5-(hydroxymethyl) furan-2-yl)-4-phenylpyrimidine-2(1H)-one derivative (6A-6P) was synthesized from the 6-(substituted aldehyde)-4-phenylpyrimidine-2(1H)-one derivative (5A-5P) through following reaction mechanisms Claisen-Schmidt, Cyclization, and Satos fusion. The structures of the synthesized compounds were elucidated by I.R.,1H-NMR, elemental analysis, and mass spectroscopic techniques. Result The synthesized compounds were screened for in vitro antifungal activity at 25, 50, 100, and 200 μg/ml concentrations. Among them, compounds 6P, 6D, and 6M exhibited significant antifungal activity that was carried out by cup plate method against fungal strain which was collected from IMTECH Chandigarh, India, against standard drug fluconazole. Compounds have been further evaluated by measuring zone of inhibition and percent inhibition. The synthesized compounds were screened for in vitro antioxidant activity using the DPPH assay, based on the AAI and antioxidant activity unit (AAU), using a combination relation between DPPH concentration and absorbance. The antioxidant strength of compounds was compared against ascorbic acid. Among them, compounds 6K, 6F, 6E, 6G, 6H, and 6M exhibited significant antioxidant activity and 6J have less active compound. The data of these synthesized compounds were submitted to the National Institute of Health, USA, under the drug discovery program of National Cancer Institute (NCI) and screened for anticancer activity at a single high dose (10−5 M) in full NCI 60 cell lines. The selected compounds have shown potent significant anticancer activity in the NCI 60 cell line screening. Conclusion A new series of pyrimidine analogues that contain furanose moiety were synthesized by Satos fusion and characterized. The synthesized compounds screened for their in vitro antioxidant, antifungal activity, as well as anticancer activity given by the derivative which has chloro, methoxy, nitro, and chloro substitution having furanose contain pyrimidine derivative that showed the most potent activity. Electronic supplementary material The online version of this article (doi:10.1186/s13588-014-0003-0) contains supplementary material, which is available to authorized users.

Palmitic Acid-Pluronic F127-Palmitic Acid Penta-Block Copolymer as a Novel Nanocarrier for Oral Delivery of Glipizide

Objective: The aim of the present study is to develop nanotechnology-based oral formulations of Glipizide to enhance bioavailability and to eliminate the frequent oral administration of the conventional dosage form. Glipizide is an antidiabetic drug with short biological half-life with limited oral bioavailability. Noval Palmitic acid-Pluronic F127-Palmitic acid (PAF127) pentablock copolymer based prolonged release glipizide nanoparticles (GN) were prepared and screened for in vitro and in vivo studies. Methods: GN was prepared using novel PA-F127 pentablock copolymer by solvent evaporation technique. The prepared nanoparticles were evaluated for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, percentage yield, drug excipient compatibility using FTIR and DSC analysis, XRD, SEM, In vitro drug release studies, stability studies and in vivo pharmacokinetic studies. Results: The results of FTIR and DSC analysis revealed the absence of drug-excipient interactions. The optimized GN1 has particle size 242.60 ± 4.20 nm, PDI 0.171 ± 0.014 and zeta potential -21.41 ± 0.462 mV. Prepared nanoparticles were spherical in shape and showed semi-amorphous characteristics. In vitro release studies showed 34.43 ± 4.8 % drug was released in first 8 h, 56.11 ± 4.12 % glipizide were released further for 24 h. The GN1 was found to be stable at 5 ± 3 oC up to three months. Pharmacokinetic studies showed that the orally administered GN1 were superior with Cmax 2.35 fold, tmax 1.6 fold, area under the curve (AUC0→∞) 3.3 fold and mean residence time (MRT) 1.2 fold as compared to pure glipizide (p < 0.05). Conclusion: The study concluded that the bioavailability of newly developed GN1 was successfully prolonged and frequent oral administration problem with conventional dosage form can be defeated for diabetes treatment.