Prabodh Chander Sharma

Pharmacological significance of triazole scaffold.

The triazole nucleus is one of the most important and well known heterocycles which is a common and integral feature of a variety of natural products and medicinal agents. Triazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, antihypertensive, antimalarial, local anaesthetic, antianxiety, antidepressant, antihistaminic, antioxidant, antitubercular, anti-Parkinson′s, antidiabetic, antiobesity and immunomodulatory agents, etc. The broad and potent activity of triazole and their derivatives has established them as pharmacologically significant scaffolds. The basic heterocyclic rings present in the various medicinal agents are 1,2,3-triazole and 1,2,4-triazole. A large volume of research has been carried out on triazole and their derivatives, which has proved the pharmacological importance of this heterocyclic nucleus. The present paper is an attempt to review the pharmacological activities reported for triazole derivatives in the current literature with an update of recent research findings on this nuclei.

Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects

In the current practices of antiinfective therapy, ciprofloxacin is a very popular fluoroquinolone having a broad spectrum of activity and diverse therapeutic prospects. The reasons for its wide use include multiresistant pathogens susceptible only to ciprofloxacin. The available clinical evidence suggests the potentially enhanced efficacy of this drug in the treatment of various community acquired and nosocomial infections, e.g. respiratory tract, urinary tract, and skin infections and sexually transmitted diseases. As compared to other agents of its class, the pharmacokinetic profile of ciprofloxacin demonstrates equivalent or greater bioavailability, higher plasma concentrations, and increased tissue penetration, as reflected in the greater volume of distribution. Various molecular modifications of this drug have been made to further improve its characteristics. Several methods of analytical determination of ciprofloxacin and its metabolites in biological fluids employing various techniques have been reported. The present article is focused on the synthetic development, pharmacotherapeutic, and analytical evaluation vistas of ciprofloxacin.

2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: Design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors

The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor.

Design of Combretastatin A-4 Analogs as Tubulin Targeted Vascular Disrupting Agent with Special Emphasis on Their Cis-Restricted Isomers

Tubulin protein is a highly imperative and feasible goal for anticancer drug discovery. Hundreds of naturally occurring, semi synthetic and synthetic antitubulin agents have been reported till now. Among these, Combretastatin A - 4 (CA - 4) is effective antimitotic agent possessing potent cytotoxicity against a panel of cancer cells, including multi-drug resistant cancer cell lines. The inadequate water solubility and inactivation of these analogs during storage limit their use as clinical anticancer agents. To overcome these shortcomings, numerous water soluble amino analogs, amino acid derivative, phosphate prodrug (CA - 4P) and cis-locked CA - 4 have been developed with distinctive attributes of antitubulin and antivascular properties in a wide variety of preclinical tumor models. Subsequently, several heterocycle based cis restricted CA - 4 analogs are being reported for antitumor activity against collection of cancer cell lines. This review recapitulates the rational design, structure activity relationship, pharmacokinetic and pharmacodynamic profile of synthesized cis restricted CA - 4 analogs.

Medicinal significance of benzothiazole scaffold: an insight view

Heterocycles bearing nitrogen, sulphur and thiazole moieties constitute the core structure of a number of biologically interesting compounds. Benzothiazole, a group of xenobiotic compounds containing a benzene ring fused with a thiazole ring, are used worldwide for a variety of therapeutic applications. Benzothiazole and their heterocyclic derivatives represent an important class of compounds possessing a wide spectrum of biological activities. The myriad spectrum of medicinal properties associated with benzothiazole related drugs has encouraged the medicinal chemists to synthesize a large number of novel therapeutic agents. Several analogues containing benzothiazole ring system exhibit significant antitumour, antimicrobial, antidiabetic, anti-inflammatory, anticonvulsant, antiviral, antioxidant, antitubercular, antimalarial, antiasthmatic, anthelmintic, photosensitizing, diuretic, analgesic and other activities. This article is an attempt to present the research work reported in recent scientific literature on different pharmacological activities of benzothiazole compounds.

New Insights into Chemistry and Anti-Infective Potential of Triazole Scaffold

Research and development for novel substances possessing anti-infective activity have attracted considerable attention due to the escalating resistance towards conventional antibiotics. Therefore, the discovery and development of effective antimicrobial drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. Triazole scaffold has been consistently rewarded as a promising versatile lead molecule with a pivotal position in modern medicinal chemistry. The literature reveals that this heterocyclic moiety has drawn attention of the chemists, pharmacologists, microbiologists and other researchers owing to its indomitable biological potential as anti-infective agents. The present communication is a cogent attempt to review the chemistry and antimicrobial activities of triazole derivatives reported in recent scientific literature. The biological profiles of these new triazole derivatives represent a fruitful matrix for further development as promising and superior anti-infective medicinal agents.

Quinazolinone Analogs as Potential Therapeutic Agents

Quinazolinone scaffold has been considered as a magic moiety possessing myriad spectrum of medicinal activities. Diversity of biological response profile has attracted considerable interest of several researchers across the globe to explore this skeleton for its assorted therapeutic significance. Various novel classes of structurally different quinazolinones have been designed and synthesized depicting potential interventions such as antibacterial, antifungal, antiviral, anticonvulsant, CNS depressant, antiinflammatory, antihistaminic, anticancer and so on. Moreover, the nucleus constitutes an integral structural component in a number of drugs currently employed in several clinical therapies. The present paper is an earnest attempt to provide an insight view on the current medicinal aspects of quinazolinone heterocycles alongwith brief discussion of their chemistry.

Novel limonene and citral based 2,5-disubstituted-1,3,4-oxadiazoles: A natural product coupled approach to semicarbazones for antiepileptic activity

Two novel series of N(4)-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N(1)-(2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enylidene)semicarbazide and N(4)-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N(1)-(3,7-dimethylocta-3,6-dienylidene)-semicarbazide were synthesized to meet structural prerequisite indispensable for anticonvulsant activity. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models. The rotorod test was conducted to evaluate neurotoxicity. Some of the selected active compounds were subjected to GABA assay to confirm their mode of action. The outcome of the present investigations proved that the four binding sites pharmacophore model is vital for anticonvulsant activity. The efforts were also made to establish structure-activity relationships among test compounds.

Synthesis and biological evaluation of novel benzothiazole clubbed fluoroquinolone derivatives.

In the present investigation, synthesis and anti-bacterial, analgesic and anthelmintic evaluation of a novel series of fluoroquinolone derivatives clubbed with benzothiazole moeity has been described. The synthesized compounds were characterised by spectral analysis (IR and 1H NMR). Preliminary results indicated that the most of the synthesized compounds demonstrated good activities against gram negative and gram positive bacterial strains. Compounds 5a, 5b, 5f and 5k demonstrated potent anti-bacterial activities. Compound 5a exhibited most potent anti-bacterial activity with MIC values of 04, 03, 08 and 15 µg/ mL against B. subtilis, S. aureus, E. coli and P. aeruginosa. Analogs 5a, 5c, 5g and 5h showed promising anthelmintic activity against Eisemia foetida in a low concentration as compared to standard drug piperazine citrate with mean paralysis time ranging 22.60 ± 2.46 to 31.60 ± 3.07 min. All synthesized compounds depicted good in vivo analgesic activity with compound 5a exhibiting the most potent activity of 55.19% inhibition of writhing in comparison to the standard drug.

A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity

Histone deacetylase inhibitors (HDACi) have been actively explored as anti-cancer agents due to their ability to prevent deacetylation of histones, resulting in uncoiling of chromatin and stimulation of a range of genes associated in the regulation of cell survival, proliferation, differentiation and apoptosis. During the past several years, many HDACi have entered pre-clinical or clinical research as anti-cancer agents with satisfying results. Out of these, more than 8 novel hydroxamic acid based HDACi i.e., belinostat, abexinostat, SB939, resminostat, givinostat, quisinostat, pentobinostat, CUDC-101 are in clinical trials and one of the drug vorinostat (SAHA) has been approved by US FDA for cutaneous T-cell lymphoma (CTCL). It is clear from the plethora of new molecules and the encouraging results from clinical trials that this class of HDAC inhibitors hold a great deal of promise for the treatment of a variety of cancers. In this review, we classified the hydroxamic acid based HDACi on the basis of their structural features into saturated, unsaturated, branched, un-branched and 5, 6-membered cyclic ring linker present between zinc binding group and connecting unit. The present article enlists reports on hydroxamic acid based HDACi designed and developed using concepts of medicinal chemistry, demonstrating that hydroxamate derivatives represent a versatile class of compounds leading to novel imaging and therapeutic agents. This article will also provide a complete insight into various structural modifications required for optimum anticancer activity.