Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.

Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals

Differently substituted flavanones were isolated from Leguminosae and their antibacterial activity was comparatively studied against methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentrations (MICs) of phytochemical flavanones to clinical isolates of MRSA were determined by a serial agar dilution method. The structure-activity relationship has indicated that 2',4'- or 2',6'-dihydroxylation of the B ring and 5,7-dihydroxylation of the A ring in the flavanone structure are important for significant anti-MRSA activity and that substitution with a certain aliphatic group at the 6- or 8-position also enhances the activity. Among the thirteen flavanones tested, tetrahydroxyflavanones with these structural characteristics isolated from Sophora exigua and Echinosophora koreensis showed intensive activity to inhibit the growth of all MRSA strains at 3.13-6.25 micrograms/ml. The present hydroxyflavanones would be useful in the phytotherapeutic strategy against MRSA infections.

Comparative Study on the Antibacterial Activity of Phytochemical Flavanones against Methicillin-resistant Staphylococcus aureus.

Liver plays a central role in the metabolism and excretion of xenobiotics which makes it highly susceptible to their adverse and toxic effects. Liver injury caused by various toxic chemicals or their reactive metabolites [hepatotoxicants) is known as hepatotoxicity. The present review describes the biotransformation of hepatotoxicants and various models used to study hepatotoxicity. It provides an overview of pathological and biochemical mechanism involved during hepatotoxicity together with alteration of clinical biochemistry during liver injury. The review has been supported by a list of important hepatotoxicants as well as common hepatoprotective herbs.

https://www.longdom.org/open-access/clinical-biochemistry-of-hepatotoxicity-2161-0495.S4-001.pdf

Clinical Biochemistry of Hepatotoxicity

Polycationic Synergistic Antibacterial Agents with Multiple Functional Components for Efficient Anti-Infective Therapy

Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles.

In the last few decades, a lot of work has been done on thiazole ring to find new compounds related to this scaffold to act as antioxidant, analgesic, anti-inflammatory, antimicrobial, antifungal, antiviral, diuretic, anticonvulsant, neuroprotective, and antitumor or cytotoxic drug molecules with lesser side effects. This review presents the up to date development on the design and development of different thiazole derivatives.

Thiazoles: having diverse biological activities

Substituted 1,3,4-oxadiazoles are of considerable pharmaceutical interest. 2,5-Substituted diphenyl-1,3,4-oxadiazoles are associated with diverse biological activities by the virtue of -N = C-O- grouping. In the view of wide range of biological properties associated with 1,3,4-oxadiazole, we have synthesized substituted derivatives of 1,3,4-oxadiazole (XIII-XXII), a versatile hydrophobic molecule possessing preliminary CNS properties, with the hope to potentiate the biological activities with lesser or limited amount of toxicities. The synthesis was based on ester substitution of substituted benzohydrazide in presence of hydrazine hydrate followed by cyclization in presence of phosphorus oxychloride. All the synthesized compounds were evaluated for their potential CNS depressant activities. Statistical analysis of the anticonvulsant, antidepressant, and antianxiety activity of the synthesized compounds on animals was evaluated using one-way analysis of variance (ANOVA). Two compounds 5-(4-nitrophenyl)-2-(4-chlorophenyl)-1,3,4-oxadiazole (XIV) and 5-(4-nitrophenyl)-2-(4-nitrophenyl)-1,3,4-oxadiazole (XV) were found to be the most promising compounds of the series in antidepressant, anticonvulsant and antianxiety activity with no neurotoxicity when compared with standard. Among the synthesized compounds, it was found that incorporation of electron withdrawing group at C2 and C5 position of the oxadiazole ring led to high degree of pharmacological activity. Thus compounds 5-(4-nitrophenyl)-2-(4-chlorophenyl)-1,3,4-oxadiazole (XIV) and 5-(4-nitrophenyl)-2-(4-nitrophenyl)-1,3,4-oxadiazole (XV) showed excellent CNS depressant activities. The result of the present investigation may encourage us to develop and/or improve similar other related compounds and it may be assumed that further modifications may produce compounds of better activity with lesser side effects.

/pdf/synthesis-and-evaluation-of-substituted-diphenyl-1-3-4-24v9tzjv1s.pdf

Synthesis and evaluation of substituted diphenyl-1,3,4-oxadiazole derivatives for central nervous system depressant activity

Transdermal administration of drugs is an another way of administration that can significantly deliver larger molecules in potent quantities that overcome the problem with the oral administration such as poor bioavailability due to first pass metabolism and sometimes responsible for rapid blood level spikes (both high and low). Drugs that are given by transdermal route may enhance the potency as well as safety of drugs. Most oftenly the medicament containing device remains in contact with the body skin that is required to reduce both the size and frequency of doses required to achieve the plasma concentrations. There are various types of transdermal patches which are further modified to increase the potential of the drug delivery. New Transdermal Drug Delivery System (TDDS) Technologies now have been developed that is considered to be helpful in rate controlled delivery of drug that are difficult to administer. This review article emphasize most of the technologies involved in better permeation through skin into an effective Drug Delivery System.

https://www.ijppronline.in/index.php/IJPPR/article/download/25/22

Nitin Kumar

Papers

Thiazoles: having diverse biological activities

Synthesis and evaluation of substituted diphenyl-1,3,4-oxadiazole derivatives for central nervous system depressant activity

Recent advancement in transdermal drug delivery system

Thiazoles, Having Diverse Biological Activities

Review on plants having hepatoprotective activity.