Current Topics in Medicinal Chemistry - Volume 16, Issue 26, 2016

Thiazole, a unique heterocycle containing sulphur and nitrogen atoms, occupies an important place in medicinal chemistry. It is an essential core scaffold present in many natural (Vitamin B1- Thiamine) and synthetic medicinally important compounds. The versatility of thiazole nucleus demonstrated by the fact that it is an essential part of penicillin nucleus and some of its derivatives which have shown antimicrobial (sulfazole), antiretroviral (ritonavir), antifungal (abafungin), antihistaminic and antithyroid activities. The synthetic importance of thiazole derivatives, its reduced forms and condensed derivatives have been increased much by their recent applications as anticancer (tiazofurin), anthelmintic, vulcanising accelerators (mercaptobenzothiazole) and photographic sensitizers. Thiazole chemistry has developed steadily after the pioneering work of Hofmann and Hantsch. Bogert and co-workers made significant contribution to expand this field. Mills established the importance of thiazole ring in cyanine dyes which is used as photographic sensitizer. Benzothiazole, a fused derivative of thiazole have also proved its commercial value. Present review describes chemical and biological importance of thiazole and its condensed derivatives with an emphasis on recent developments.

Nitrogen containing heterocyclic rings with an oxygen atom is considered as one of the best combination in medicinal chemistry due to their diversified biological activities. Isoxazole, a five membered heterocyclic azole ring is found in naturally occuring ibetonic acid along with some of the marketed drugs such as valdecoxib, flucloxacillin, cloxacillin, dicloxacillin, and danazol. It is also significant for showing antipsychotic activity in risperidone and anticonvulsant activity in zonisamide, the marketed drugs. This review article covers research articles reported till date covering biological activity along with SAR of fused isoxazole derivatives.

The three heteroatoms containing five membered heterocycles such as thiadiazoles have been extensively studied due to their important pharmacological activities. The thiadiazole nucleus is an important class of compounds for new drug development. The chemical and biological behavior and synthesis of thiadiazole derivatives have gained much importance in last few decades. This review article provides up to date information about exploration of new methods, developments, synthetic strategies, and their diverse pharmaceutical activities.

The global tuberculosis epidemic and emergence of drug resistance call for intensive research on new antimycobacterial agents. Recent development is focused mainly on heterocyclic molecules. In many cases, introduction of sulphur has improved antimicrobial activity; many drugs feature a sulphur heterocycle. Thiophene derivatives and thiadiazoles including derived ortho-condensed heterocycles have been found to have a wide range of biological activities. This review highlights the recent progress in the field with a focus on whole-cell antimycobacterial activity of the agents as well as targeting of enzymes from Mycobacterium tuberculosis. Some of the compounds have exhibited high activity with submicromolar minimum inhibitory concentrations including activity against drug-resistant strains and/or IC50 values for a range of enzymes as their targets (InhA, dehydroquinase, Pks13, carbonic anhydrases, DprE1). Mechanisms of action, toxicity, and structure-activity relationships are also discussed. Several compounds have exhibited promising in vitro and in vivo activities and safety profiles, thus constituting novel, promising leads.

Benzimidazole is a heterocyclic aromatic organic compound which has been an important pharmacophore and privileged structure in medicinal chemistry. Substituted benzimidazoles have considerable interest as compounds with a wide spectrum of biological activity and low toxicity. Benzimidazole derivatives are structurally related to purine nucleoside bases, which allow them to interact easily with the biopolymers of the living systems. Different substituted benzimidazoles have an extensive range of biological activities including: antiviral, antifungal, antimicrobial, antiprotozoal, antiinflammatory, anticancer, antioxidant, anticoagulant, antidiabetic and antihypertensive activities. Infectious diseases are those whose incidence in humans has increased during the past few decades. They cause suffering and death and an enormous financial burden. Antimicrobial drugs have saved the lives of millions of people. However, the dramatic increase in drug-resistant microbes is threatening to reverse medical progress of the past 50 years. Benzimidazoles are very effective compounds with respect to their bacteria inhibitory activity. Biochemical and pharmacological studies have showed that these molecules are effective against various strains of microorganisms. Some benzimidazole compounds inhibit the biosynthesis of ergosterol, required in the cell membrane of fungi and protozoa and a useful target for antifungal drugs. The result of many efforts to develop new molecules for effective antimicrobials reveals that the benzimidazoles are still one of the most versatile class of compounds against microbes.

The imidazo[1,2-a]pyridine scaffold is recognized as a privileged structure as it represents a promising area for identification of lead structures towards the discovery of new synthetic drug molecules. Several commercial drugs such as Zolpidem, Olprinone, Soraprazan and many other compounds in biological testing and preclinical evaluation, illustrate the wide therapeutic spectrum in this class of drug scaffolds. The present manuscript represents the assimilation of literature pertaining to medicinal aspects of this pharmacophore including the structure-activity relationships.

The fascinating chemical properties of N-heterocyclic carbene (NHC) complexes showed them to be a suitable class of complexes to be investigated for their applications as drugs in the treatment of the infectious disease or cancer. In particular, the great structural versatility provided a library of compounds with a low cytotoxic profile, suitable candidates as new anticancer agents. Most of these complexes have shown higher cytotoxicity than cisplatin. In the present review, the medicinal applications of copper(I)- and silver(I)-NHC complexes are summarized. Specifically, azolium precursors and related Cu(I)- and Ag(I)-NHC complexes of functionalized and non-functionalized imidazole-, and benzimidazole-based NHC complexes studied as an alternative to cisplatin as chemotherapeutic agents are reviewed. An outline of the most significant chemical features is presented: copper(I)- and silver(I)-NHC complexes tested as anticancer drugs have been reported and a description of structure-activity relationships was made as far as possible.