Thursday , 15 November 2018

BENZOXAZOLE: THE MOLECULE OF DIVERSE PHARMACOLOGICAL ACTIVITIES

About author :
Ramesh Dhani
Department of Pharmaceutical Chemistry
JNTUA-OTRI, Anantapur, India
E-mail: dhanipharmachem@gmail.com
ABSTRACT:
Oxazole is a heterocyclic organic compound that has a five-member ring molecular structure, containing oxygen, nitrogen as heteroatoms at its 1, 3-positions.  Benzoxazoles are derivatives of oxazoles. Benzoxazoles is a planar molecule with conjugated p electrons sextets in the cyclic systems. The lone pair of electrons on nitrogen, which is coplanar with heterocyclic ring and therefore not involved in delocalization, confers weakly basic properties. Targets containing the benzoxazole moiety, either isolated from plants or accessed by total synthesis have remarkable biological activities.  For example, antimicrobials, polycyclic antibiotics, antiparasitics, anti-inflammatory, H2-antagonists contain the benzoxazole fragment. Benzoxazole a lead nucleus for future developments to get safer and effective compounds.
Key words: Benzoxazole, Oxazole, Flunoxaprofen, Antibiotics, Antiparasitics, Diuretic.
Content :                                   
Oxazole is a heterocyclic organic compound that has a five-member ring molecular structure, containing oxygen, nitrogen as heteroatoms at its 1, 3-positions.  Benzoxazoles are derivatives of oxazoles. Benzoxazole (M.P. 27-30°C; B.P. 182°C) is an aromatic organic compound with a molecular formula C7H5NO, a benzene-fused oxazole ring structure; appearance is white to light yellow solid and an odour similar to pyridine. Other name of benzoxazole is 1-oxa-3-aza-1H-indene.  It is used primarily in industry and research. Benzoxazoles is a planar molecule with conjugated p electrons sextets in the cyclic systems.The lone pair of electrons on nitrogen, which is coplanar with heterocyclic ring and therefore not involved in delocalization, confers weakly basic properties. Being a heterocyclic compound, benzoxazole finds use in research as a starting material for the synthesis of larger, usually bioactive structures.  It is found within the chemical structures of pharmaceutical drugs such as flunoxaprofen. Its aromaticity makes it relatively stable, although as a heterocycle, it has reactive sites which allow for functionalization. Oxazole and its derivatives are used as building block for biochemicals and pharmaceuticals as well as in other industrial applications such as pesticides, dyes, fluorescent brightening agents, textile auxiliaries and plastics. The benzoxazole nucleus is an important heterocyclic moiety and their derivatives display a wide variety of important biological activities such as antimicrobial, anti-inflammatory, anti-viral, anti-histaminic, herbicidal, anthelmintic, anti-cancer, hypoglycemic, 5-HT3 agonist, diuretic, and 5-HT3 antagonist, uricosuric.
Bioloical activities 
Targets containing the benzoxazole moiety, either isolated from plants or accessed by total synthesis have remarkable biological activities.  For example, antimicrobials, polycyclic antibiotics, antiparasitics, anti-inflammatory, elastage inhibitors, H2-antagonists contain the benzoxazole fragment. The novel antibacterial agent containing the benzoxazole system,“Boxazomycin B” is reported by suto and turner.  The antibiotic containing benzoxazole ring, “calcymycin” and the anti-inflammatory agent, “Benoxaprofen” are also obtained by synthetic routes. Chloroxazone a chloroxazolidinone has muscle relaxant property and used for reduction of painful muscle spasms in medicinal and orthopedic disorders.These examples highlight the level of interest in new synthetic approaches to benzoxazole derivatives. These classes of compounds are considered to be important in view of their varied pharmacological properties.  The following literature survey throws much light on the pharmacological significance of benzoxazole derivatives.  For the sake of convenience it is presented on the basis of their biological activity.
1. Benzoxazoles as antimicrobial agents
V. Sundari and R. Valliappan synthesized new 3,5-diaryl-4-(2-ethoxy benzoxazol-2-yl)-tetrahydro-1,4-thiazine-1,1-dioxides and ,2,6-dimethoxycarbonyl-3,5-diaryl-4-(2-ethoxybenzoxazol-2-yl)-tetrahydro-1,4-thiazine-1,1-dioxides and they were tested for their antibacterial and antifungal activities.These compounds inhibited the growth of bacteria and fungi at a minimum concentration of 25 mg/ml when compared against the standard Norfloxacin (V. Sundari et al., 2004).
Ozlem Temiz Arpaci reported the synthesis, QSARs analysis and in vitro antifungal activities of different 5- or 6-methyl-2-substituted benzoxazoles against the fungus Candida albicans (Ozlem Temiz et al., 2001).
Aki-Sener et al., Synthesized new antimicrobial active N-(2-hydroxy-4-nitro phenyl)-P-substituted benzamides and phenylacetamides analogues which were prepared by 2-step procedure from corresponding carboxylic acids as possible metabolites of benzoxazoles (Aki-Sener et al., 2004).
A series of 2,5- and / or 6-substituted benzoxazoles holding cyclohexyl or cyclopentyl moieties at position 2 and 5-or 6-substituted-2-cyclohexyl-aminomethyl benzoxazoles were synthesized by Ismail Yalcin et al.  In order to examine their antimicrobial activities against different gram positive, gram negative bacteria and the yeast C. albicans.  Feasible structure activity relationships were also determined in these studies (Ismail Yakin et al., 1998).
Structure-activity relationships reveal that substitution of position 2 on the fused heterocyclic system with a cyclohexyl ring causes increased antimicrobial activity compared to cyclopentyl substitution.
Seyhan Ersan et al., reported the synthesis and antimicrobial activity of some new 2-[(a-methyl benzylidene) hydrazine] benzoxazole derivatives. Antimicrobial activities of the compounds were investigated by the microdilution susceptibility test in Mueller-Hinton broth and Sabouraud liquid medium.Test organisms: Staphylococcus aureus and Enterococcus faecalis as gram positive bacteria, E. coli, and Pseudomonas aeruginosa as gram negative bacteria, and Candida albicans, Candida stellatoidea, Candida parapsilosis and Candida pseudotropicalis as yeast (Seyhan Ersan et al., 1997).
2. Benzoxazole as anti-viral agents
Bahadur and Pandey reported the synthesis and antiviral activity of P-(2-benzoxazoly) phenoxy acetic acid hydrazide  and the corresponding arylidene hydrazide.
The compounds were found to exhibit a significant antiviral activity in vitro (Surendra Bahadur et al., 1981).  Aysegul Akbay et al., investigated the synthesis of 2, 5, 6-substituted benzoxazole derivatives and evaluated for in vitro anti-HIV activity.
3.Benzoxazoles as 5-Ht3 Agonists
Several modified 2-piperazinyl benzoxazole derivatives which exhibit an agonistic effect on gastrointestinal motility, were synthesized and their effects on the contraction of guinea-pig ileum were examined (Yasuo Sato et al., 1998).
4.Benzoxazoles as anti-histaminic agents
Noyanalpan et al., reported the synthesis and antihistaminic activity of 5-nitro-2-(P-substituted benzyl) benzoxazole derivatives (Noyanalpan et al., 1986).
Jestsuya Makino et al., reported the preparation of benzoxazole derivatives of the type from ethyl-6-hydroxybenzoxazol-2-carboxylate and 2-(chloromethyl) quinodine.
Conclusion : 
This review thus gives an overview of therapeutic and diverse biological properties of the benzoxazoles and its derivatives and the availability of varied drugs in the market containing the heterocyclic ring. Therefore, these observations have been guiding for the development of new benzoxazole nucleus, which can be a lead nucleus for future developments to get safer and effective compounds. Thus this paper proves to be significant for further research work on the bioactive oxazole ring.

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