Abstract: Thiadiazoles are an important class of heterocyclic compounds that exhibit diverse applications in
organic synthesis, pharmaceutical and biological applications. They are also useful as oxidation inhibitors, cyanine dyes, metal chelating agents, anti-corrosion agents. Researchers across the globe are working on this moiety due to their broad spectrum of applications of thiadiazolechemistry. This article provides information about developments, exploration, synthetic strategies, techniques for the synthesis of thiadiazoles and their diverse biologicalactivities, structure-activity relationship of the compounds and physical properties. This article is an important tool for organic and medicinal chemists to develop newer thiadiazolecompounds that could be better agents in terms of efficacy and safety.
Chemical properties of 1,3,4-thiadiazole have been reviewed in last fast five year. However, usefulness of 1,3,4-thiadiazole has a privileged system in the medicinal has been promoted advance on therapeutic potential of the system. This review provides a brief summary of medicinal chemistry of 1,3,4-thiadiazole system. The highlight some example of 1,3,4- thiadiazole containing the drug substance in the current literature. Several five membered aromatic systems having a three heteroatom at symmetrical position such as thiadiazole owing a several pharmacological activity. It covers the most active thiadiazole derivative and structural activity relationship of the most potent compounds. It acts as an important tool for medicinal chemist to develop a newer compound possessing the thiadiazole moiety that could be better agents in term of efficiency and safety.
The review was carried out to discuss in detail about the substituted 1,3, 4 thiadiazolecompounds. heterocyclic compounds such as thiazoles, thiadiazoles, indoles, oxadiazoles, benzisoxazoles and pyrroles have been successfully used as Antibacterial, Anticancer, Antipyretic, Schistosomicidal, Hypoglycemic, Antihypertensive, Anti-tubercular, Anti-inflammatory and Anti-HIV agents. All large number of organo-sulfur compounds occur in living and non- living object. They belong to open chain, alicyclic, aromatic and heterocyclic types of compounds containing sulfur atoms or atoms as a part of chain/ring or both in the structure. In this review briefly study about the Structure and reactivity of 1,3,4-thiadiazoles, Characteristic reactions, Characteristic features of 1,3,4-thiadiazole, Methods of synthesis, biological interest. And in this review can be concluded that many researches had investigated on substituted thiodiazole compounds having the biologicalactivities.
Heterocyclic compounds are organic compounds that contain a ring structure containing atoms in addition to carbon, such as sulfur, oxygen or nitrogen, as the heteroatom. Several five membered aromatic systems having three hetero atoms at symmetrical position have been studied because of their interesting physiological properties [1-8], such as azole, pyrole, thiazole, thiadiazole, oxadiazole, triazene etc. and they also exihibits wide variety of biologicalactivities. Thiadiazole is a heterocyclic compound featuring both two nitrogen atom and one sulfur atom as part of the aromatic five membered ring. Thiadiazole and related compounds are called 1, 3, 4-thiadiazole (two nitrogen and one other hetero atom in a five-membered ring). The others four isomeric forms of thiadiazole are occurred in nature as 1,2,3-thiadiazole; 1,2,5-thiadiazole; 1,2,4-thiadiazole. 1,3,4-thiadiazoles are important compounds in medicine, agriculture, and in many fields of technology. A large number of thiadiazoles have been patented in the medical field for the treatment of a wide variety of diseases and some of them have become commercial products. A large number of thiadiazoles have been patented in the medical field for the treatment of a wide variety of diseases and some of them have become commercial products compounds in medicinal chemistry because of its therapeutic values. It is also known to have unique antibacterial and anti-inflammatory activities. Differently substituted thiadiazole moieties have also been found to have other interesting activities such as analgesic, antimicrobial, anti- tubercular, anticonvulsant and anti-hepatitis B viral activities. Due to presence of –N=C-S moiety in its structure 1,3,4-thiadiazoles exhibit various biologicalactivities .
The chemistry of metal-drug interaction is significant and becoming popular. The efficacy of the drugs on complexation with metal ion is enhanced in many cases. This review article covered some of the recent literature of the metal-ion interaction with selected quinolones and their comparative biologicalactivities with respect to free quinolones. The quinolones represent a diverse class of bactericidal agents with multiple applications in ocular infectious diseases. Their mechanism of action particularly targets to stop bacterial DNA synthesis and structural modification in different generations of these compounds have led to improved bioactivity against wide coverage of resistant species. Transport of organic ligands into bacterial cells can be facilitated by the formation of metal complexes. In most of the quinolone-metal complexes, due to the ring carbonyl group at position 4 and one of the oxygen atoms of carboxylato group at position 3, the quinolones act as bidentate ligands. The synthesis of the complexes does not require any extreme reaction conditions rather most of the complexes have been formed by simple stirring with corresponding salts at room temperature. We can conclude that the mode of action of these drugs and their metal complexes were extensively studied in the past, but there are still several questions to be answered hence effective research in the field is still the need of the hour.
1,3,4-Thiadiazole and their derivatives exhibit a broad spectrum of biological effectiveness like antimicrobial, antiinflammatory, antitubercular, antidiabetic, anticancer, antidepressant, anti- parkinson, hypoglycaemic, anti-hypertensive and diuretic activity. This review provide a broad view of chemistry of 1,3,4- thiadiazole system and it includes the literature survey on methods of preparation and pharmacological activities of 1,3,4-thiadiazole moiety. As a result, compounds containing 1,3,4-thiadiazole were attracted much attention in the field of medicines.
Chrysin is a naturally occurring flavonoid, mainly found in honey, propolis and in many plant species. Owing to its multiple pharmacological properties such as antioxidant, anti-inflammatory, anti-allergic, anti-diabetic, anti- estrogenic, antibacterial, neuroprotective activity and antitumor activities, chrysin has become the foremost candidate among flavonoids in recent years. Chrysin derivatives had also seen potential applications in anticancer drug delivery. Due to issues such as bioavailability and absorption associated with Chrysin, its therapeutic benefits remained nascent unlike other flavonoids. To overcome these limitations and to obtain compounds with improved efficacy and developing more active drugs efforts had been made by designing analogs and conjugates of Chrysin. The target of the current review is to articulate the recent progress in research on synthesis and pharmacological activities of Chrysin derivatives. Additional information on the basic chemical reactivity of Chrysin, its bioavailability and toxicity is also presented in this article.
N-halo reagents are widely used in fine organic synthesis. These include N-halo derivatives of amines, amides, imides, urea, saccharin, sulphonamides, sulphinimides etc. Depending on the conditions, a number of highly reactive intermediates can be formed including halogen radicals, halogen cations, halogen anions, N-radicals, N-cations, N- anions etc. Consequently, N-halo compounds have the potential to promote important reactions such as halogenation, oxidation and protection as well as formation of C -X, C -O and C=O bonds. In addition to the numerous organic and inorganic halogenating agents, N-halo reagents play an important role in the chemistry of natural compounds.
In 1986 the first chemists took advantage of microwaves for heating chemical reactions, in the same way they had been heating food for decades . In 1986 Gedye, who worked at Laurentian University, published that reaction rates increased significantly when heated by a domestic Toshiba microwave (on power 7).The reaction presented included acid hydrolysis of an amide, KMnO4 oxidation, esterification and SN2 substitution. Months later Giguere and Majetich reported the use of microwave ovens to perform pericyclic reactions. Microwave heating has led to cleaner, faster, and often higher yielding reactions. During the last two decades, the activity in this new technique has experienced exponential growth and has been extensively reviewed . Kappe and Dallinger have reported the impact of microwaves on drug discovery . Even microwave-assisted reactions under solvent-free conditions promoted the synthesis of Zincke’s salt and its conversion to chiral pyridinium salts in water . Moreover, Varma and co-workers have reported the drug discovery by using aqueous microwave chemistry . Microwave- assisted organic transformations using benign reaction media have also been reported [8, 9]. A survey of the literature shows that there is no report on the microwave assisted [2+ 2] cycloaddition reactions of ketenes to >C=C< of the 3,4-dihydropyrimidone. Hence In continuation of our work [10,11] on the reactions of 3,4- dihydropyrimidones, we report the synthesis of the novel heterocyclic compounds, 2(a-d) by the microwave assisted [2+2] cycloaddition of chloroketene to the >C=C< of the 3,4-dihydropyrimidinones 1(a-d).The novel heterocyclic compounds 3(a-b) were synthesised by the microwave assisted [2+2] cycloaddition of dichloroketene to the >C=C< of the 3,4-dihydropyrimidinones, 1a and1c. We also report on the antimicrobial activity of the novel heterocyclic compounds, 2(a-d) and 3(a-b) and the cytotoxic activity of the novel heterocyclic compounds 2(b)& 3(b).
Several five membered aromatic systems having three heteroatoms at symmetrical positions such as thiadiazoles have been studied extensively owing to their interesting pharmacological activities. This review article covers the most active thiadiazole derivatives that have shown considerable biological actions such as antimicrobial, anti-inflammatory, anticancer, anticonvulsant, antidepressant, antioxidant, radioprotective and anti-leishmanial. This review also discusses the structure-activity relationship of the most potent compounds. It can act as an important tool for medicinal chemists to develop newer compounds possessing thiadiazole moiety that could be better agents in terms of efficacy and safety.
in tumour cell lines (Liao, 1982). Willingham et al. (1981) found brusatol to be an extremely potent inhibitor of protein synthesis in rabbit reticulocyte preparations and also suggested that brusatol inhibits the ribosomal peptidyl transferase reaction of the elongation stage in protein synthesis. Bruceantin has been shown to have a similar mechanism in the yeast Saccharomyces cereviseae (Fresno et al., 1977). Hence it is concluded that in P. falciparum, as in eukaryotic cells, quassinoids are potent inhibitors of protein synthesis and that this is most likely due to direct effects upon the ribosome rather than secondarily as a result of inhibitory actions on nucleic acid (mRNA and tRNA) synthesis. Quassinoids have also been shown to affect other cellular processes including DNA polymerase, messenger and transfer RNA polymerase, purine synthesis and dihydrofolate reductase (Hall et al., 1982). Inhibitory effects upon oxidative phosphorylation and the blocking of aerobic respiration have been reported (Hall et al., 1982). Chan et al. (1992) have shown that the cytotoxic activity of quassinoids from Eurycoma longifolia is not mediated through DNA cleaving properties. Glycolysis appears not to represent a significant target for the action of quassinoids in F. falciparum (Kirby et al., 1992). The effects of ailanthinone, bruceine B and glaucarubinone at concentrations 10 times their ICjq values on lactic acid production by P. falciparum has been investigated and the results indicated that they had no significant effect on glycolysis (Kirby et al., 1992).
In this chapter, a brief introduction to the biological activity of 2H-1-benzopyran-2-ones, Quinazolines, Quinazolinones, Selenadiazolo benzimidazoles, Thiadiazolo benzimidazoles, Selenadiazolo Xathones, Hexahydroxathenes, Pyrazoles and Dihydropyrimidin-2(1H)-ones is discussed. The above molecules are important in medicinal applications and they are incorporated in several drugs. Applications of these drugs prompted to synthesize the heterocyclic molecules by employing new reagents under conventional method and also under green techniques like solid state method and microwave irradiation.
Schiff bases are an important class of ligand in coordination chemistry. Schiff bases derived from hydrazones and aroyl hydrazines have been widely used as ligand for the synthesis of transition metal complexes. Schiff bases or their metal complexes have many applications in different fields Hydrazones, heteroaroyl hydrazones ligands and their metal complexes are biologically active. Heteroaroyl hydrazones forms stable metal complexes with transition metal ions and inner transition metal ions due to complexing ability of ligand through keto-enol tautomerism and availability of other donar sites in the ligand i.e. isonicotinoyl hydrazide is one of the drug [n chemotherapy of tuberculosis. Due to its biological potency, pharmacological properties and synthetic flexibility of Schiff base derived from isonicotinic acid hydrazide. The aim of present investigation is to synthesize various transition metal complexe of Schiff base derived from 2-hydroxy-5-Bromo -3-nitroacetophenone and isonicotinoyl hydrazide.
Antibacterial screening for all the synthesized compounds 5a-5l, against two Gram-negative bacteria i.e. E. coli (MTCC 119), P. aeruginosa (MTCC 7453) and two Gram-positive strains i.e. B. pumilus (MTCC 7411), S. aureus (MTCC 96) was carried out. The antibacterial evaluation of synthesized compounds was carried out by minimum inhibitory concentration (MIC) method. Microorganisms were inoculated and incubated according to procedure provided by NDRI, Karnal. The bacterial cultures were grown on nutrient agar plate and kept at 4°C. The experimental MIC values of the target compounds against selected bacterial strains have been shown in table 1.
The synthesis involves reaction of substituted salicylic acid hydrazide 1 with substituted benzoyl chloride 2 which resulted in the formation of substituted diacyl hydrazines (3a-f). Cyclization of substituted diacyl hydrazines was carried out using Lawesson reagent, which resulted in formation of 2,5-Disubstituted-1,3,4-thiadiazoles (4a-f). 2,5- Disubstituted-1,3,4-thiadiazoles undergo reaction with different aromatic aldehydes to form different Schiff bases. The compounds were purified by repeated recrystallization from ethanol and then dried under vacuum [24, 25]. The synthetic scheme illustrates the way used for the synthesis of target compounds (Figure 1). The structures of compounds were characterized by IR, 1 H NMR, 13 C NMR and elemental analysis.
All the compounds exhibited significant anti-inflammatory activity. Among the ten compounds, the synthesized compounds substituted with hydroxyl benzaldehyde 7a,7b and 7c, nitrobenzaldehyde 7d,7e and 7f and dimethyl amino benzaldehyde 7i were found to be more active as that of standard drug Diclofenac sodium and compound substituted with trimethoxy benzaldehyde 7j was moderately active. Moreover, all the compounds exhibited moderately potent antibactierial and antifungal activity.
Thiazolidinone is a saturated form of thiazole with carbonyl group on fourth carbon and has been considered as a magic moiety which posses almost all types of biological activites. In thiazolidinone ring, substitutions can occur on 2, 3 and 5 positions but substitution on second position carbon atom ring exert valuable effect on structure and property of thiazolidinones. Thiazolidinone, an important „„privileged scaffold,‟‟ is a very attractive target for combinatorial library synthesis because of their structure activity relationship and is an important class of N and S containing heterocycles, which are widely used as key building blocks in the field of drugs and pharmaceutical agents.  Further, the presence of the N–C–S linkage in the thiazolidinone is also responsible for nematocidal, fungicidal, antibacterial and antiviral activities In addition, the spiro[indole-thiazolidine] system.(figure 2)
Heterocyclic compounds are the cyclic organic compounds which contain at least one hetero atom, the most common heteroatoms are the nitrogen, oxygen and sulphur but heterocyclic rings containing other hetero atoms are also widely known. Carbocyclic compound a cyclic organic compound containing all carbon atoms in ring formation. Heterocyclic compounds considered one of the vital classes of organic compounds, which are used in many biological fields, due to it is activity in multiple illnesses. Biological molecules such as DNA and RNA, chlorophyll, hemoglobin, vitamins and many more contains the heterocyclic ring in major skeleton. There are a lot of heterocyclic compounds which are have application in many common diseases such as; triazine derivatives have been used as antimicrobial herbicides, urinary antiseptics and anti-inflammatory agents. Benzimidazole derivatives have been reports to possess wide range of biologicalactivities such as antibacterial, antifungal, antiviral and anthelmintic, etc. .
A solution of compounds 5a-d (10 m mole) in acetic anhydride (15ml) was boiled under reflux for 2h. The resulting solution was poured onto crushed ice , and the product that separated out was filtered off, washed with solution of sodium hydrogen carbonate followed by water and then dried. The products were recrystallized from a proper solvent. Saccharinyl (N’- benzoyl methyl) acetamide(7)
The results of antifungal studies are shown in Table- 3. It is observed that all the three organic compounds (1,2 &3) played significant role on pathogenic fungi Aspergillus fumicaytus, Fusarium spp, Trichophyton rubrum and Penicillium spp. The growth control effect was very high than the standard Amphotericin-B. The effective inhibitory activity was observed on all the two days of incubation period taken for the study. It seems from the results that sulfur in the organic compounds plays a significant role in the inhibition activity.