"Synthesis and Biofunctional Evaluation of Novel Isoxazole, C-Nucleoside and Thioxopyrimidine Derivatives"

Thioxopyrimidines are an important class of compounds in the fields of biology and chemistry that play significant roles in drug discovery, nucleic acid chemistry, enzyme inhibition


INTRODUCTION
Organic chemistry's thiopyrimidines constitute an intriguing subject with a wide range of practical and research applications.They make adaptable building blocks for the synthesis of diverse compounds with specific features because of their distinctive sulfur-containing structure.In contrast to regular pyrimidines, such as uracil or cytosine found in DNA and RNA, thiopyrimidines contain sulfur atoms in place of oxygen atoms within the ring. 21Glucosides are other organic substances that can be found in both plants and animal species.They are essential for producing organic molecules more readily soluble in water and reducing the toxicity of aglyconemoieties.It has been discovered that the metabolic and antitumor properties of glucosides.The glucosylation reaction is essential for the production of complex glucosides, oligosaccharides, complex carbohydrate conjugates, and biomolecules based on carbohydrates.They serve as the main carrier for the aglycone moiety and act as a pharmacophoric group which helps target cells in recognizing the structure.Glycosides are consisting of a sugar remnant that links up to moiety associated with aglycone, where the non-carbohydrate group is links the sugar molecule in glucosides [1][2][3] .Several glycosides are utilized in the production of sweetening agents, additives for food, non-ionic surfactants and antibiotics for use in pharmaceuticals, synthetic glycogen biosynthesis primers, and cosmetics 4 aglycones associated to glucose show significant effects involving cytotoxicity, antitumor, anti-inflammatory, anti-carcinogenic, 5 antiviral, antifungal, 6 antimicrobial activity.molluscicidal, and anti-hypercholesteremic. 7 steroidal glycosides have been reported to exhibit plant growth stimulant activities 8 .
The alcohols and thiols are equivalent to each other with different functional groups in both, the -SH of thiols have various useful biological activities therefore studied with scientific interest.Due its reactive nature towards free radicals plays a significant role in biological activities as well as it protecting against harmful ionizing radiation and have significant role in metabolism of drugs in body. 20The higher Molecular weight thiols are important ingredient of natural flavor's, While lower molecular weight thiols with unpleasant smell are widely used of the diagnosis of extreme thyroid storm.Thiopyrimidine scaffold abundantly present of pharmaceutical products with antiviral, analgesic, and most important compounds used in the non-destructive therapy of thyroid disease; they are the treatment of choice in pregnancy and adolescence.
Pyrimidine compounds recently came to light to have antimicrobial and antiinflammatory effects, antitumor and anticancer activities [9][10][11][12] .Pyrimidine plays a crucial role in nucleic acids and serves as a fundamental building block in numerous pharmaceutical products. 17rimidinethione are frequently incorporated into metal-based medications intended to specifically address various biological processes or medical conditions. 18Previously we have investigated various biological activities of these benzisoxazole derivatives aspromising class of heterocyclic compounds and show biological and pharmacological properties such as antitumor, antithrombotic, analgesic antioxidant, antimicrobial, anticancer, anticonvulsant, antipsychotic and anti-inflammatory agents [13][14] .With the broad biological and pharmacological uses of O-glucosides, thiopyrimidines, benzisoxazolesandextended research on heterocyclic compounds previously carried out, we produced a variety of pyrimidine and O-glucoside and examined their abilities to fight off microbes. 20

RESULTS AND DISCUSSION
Thiopyrimidines and their O-glucosides were successfully synthesized with high yields, as outlined in Schemes I and II.The structural confirmation of the products was accomplished through spectral and elemental analyses and Melting point and boiling and optical properties which are given in Table 1, 2 including FT-IR was taken at 4000 cm -1 to 500 cm -1 confirms functional groups and bonds presentshow in the range of 958-1271 cm -1 .Noabsorption band at 1175-1140 cm -1 shows the polysaccharide's glycoside linkage, which shows the breakage of linkage.Sharp bands at 1271 and 1371 cm -1 were obtainedbecause ofester linkage of formed glycoside.A band at 3331 cm -1 is due to -OH groups.Shar p absor ption peak at 2890-3000 cm -1 correspond to the alkyl CAH stretched oscillations.Bands at 1640 and 1677 cm  1, 2 confirmers molecular mass and structure of compounds.The Compound evaluated for Biological activity, as antibacterial and antifungal on species such as Candida albicans and Aspergillus niger (fungal) and S. aureus and E. coli (Bacterial) using different concentrations of (6a-j) and screening results showed excellent (22-28mm), moderate (15-21mm) and poor (11-14mm) growth against the both organisms.The different zone of Inhibition by the action of compound against bacterial and fungal strains show in Table 3.

Antimicrobial activities
All Media and agar required for the bacterial and fungal growth are of highest grade and from Indian supplier.Synthesized compounds(6a-j)shows huge antibacterial and antifungal action on different species of bacteria and fungi therefore examined for antibacterial activities by using the cup plate procedure counter to S. aureus and E. coli at concentration of 150 µg/mL in DMF.The screening gave excellent outcomes.(13-16mm),(9-12mm) and inactive (below 8mm) growth counter to both the microbial strain.The antibacterial action of (6a-j) and derivatives is due inhibition of bacterial RNA synthesis and replication of DNA which inhibits the proteins syntheses. 21The compound also dispute the bacterial cell wall by interacting with lipoproteins and leads to leakage of cellular fluids which is responsible for the death of bacteria. 19ntifungal activity was determined by the same cup-plate method counter to Candida albicans and Aspergillus niger at a concentration of 100 µm/mL in DMF.The screening results showed excellent (22-28mm), moderate (15-21mm) and poor (11-14mm) growth against the both organisms.Norfloxacin 100 µg/mL was standard against E. coli and S. aureus, and Griseofulvin 100 µm/ mL was standard against A. niger and C. albicans Table 3.The mechanism of action on fungal speciesis same as that for bacteria, one of the important essential ergosterol 22 which need for fungal cell wall synthesis is inhibited by (6a-j) leds to antifungal activity of the Compound.

CONCLUSION
The successful synthesis of isoxazole, C-Nucleoside, and thioxopyrimidine compound, characterized and confirms by IR, NMR and other instrumentation techniques.Our research has demonstrated the potential of this compound as development of novel antimicrobial agent.This exploration is driven by their distinct pharmaceutical applications, characterized by specified mechanisms of action and significant biological activities, against bacterial and fungal strains.As a result, pharmaceutical companies have ample opportunities to further explore novel and potent therapeutic agents with promising potential.