Current Organic Chemistry - Volume 18, Issue 20, 2014

In continuation with the earlier “Thematic Series - Bioactive Heterocycles, Part 1', this is the second Thematic Series on this vibrant area of bioactive heterocyclic entities. Diversity-oriented synthesis (DOS) is a thriving field involving the preparation of chemical libraries of versatile small molecules for biological screening. The last decade has witnessed tremendous progress in the field, with continued emphasis on structural and functional diversity for DOS library construction. A number of recent reviews have updated the synthetic organic chemists on this topic, including recent successes of biologically active molecules obtained from DOS compound collections. The role of multifaceted coumarin synthesized by DOS, the bioisostere of naturally occurring Calanolide A and B, as a privileged class of compounds was proven to be significant for dormant tuberculosis. The therapeutic significance of guanidines synthesized by DOS as antiprotozoal and antiparasitic is well-established while its significant role in neglected tropical diseases (NTDs), such as human african trypanosomiasis, chagas disease, leishmaniasis, buruli ulcer,echinococcosis, taeniasis/cysticercosis, lymphatic filariasis and onchocerciasis has been summarized extensively. The importance of 1-aryl propargylic alcohols as a key building block in the constructions of bioactive five- and six-membered heterocycles has been scrutinized. In the area of peptidomimetics, a new class of amphiphilic peptides, both in linear and rigid form and its nanoparticles was synthesized for biomaterial sciences and biomedicines study. Nano-composites have exceptionally high surface to volume ratio. The role of nanocomposites in the synthesis of bioactive precursors via green technology assisted by ultrasound methodology might prove worthy for its application in drug discovery. The contribution of various authors across the globe is quite noteworthy to make this issue very rich for all who are working at the interface of chemistry and biology. Taken collectively, Bioactive Heterocycles embodies a broad, vibrant and continual growing scientific area with this Thematic Issue is highlighting recent advances in the field. As a Guest Editor of this Thematic Issue (Part 1 & 2), I would like to thank authors for their excellent scientific contributions and make this issue successful. I am also indebted for secretarial assistance from Dr. Atul Manvar and other research scholars of my research group at the National Facility for Drug Discovery Centre, Saurashtra University, Rajkot. Lastly, I thank Bentham Science Publishers for their excellent professional support.

Over one billion people worldwide are afflicted by a group of 17 infectious diseases, known as the neglected tropical diseases (NTDs), reaching mainly undeveloped countries that suffer with a lack of economic incentive, research and policy for new drug discovery. Compounds with guanidine moiety are privileged structures and are attractive as scaffold for the discovery of new drug candidates. This functional group is an important pharmacophore moiety in several therapeutically active compounds. Guanidine-containing heterocycles have been reported to exhibit different biological properties including antiprotozoal and antiparasitic activity such as mebendazole and pyrimethamine used in current therapeutics. The present review covers the progress of guanidine derivatives for NTDs (Human African Trypanosomiasis, Chagas Disease, Leishmaniasis, Buruli Ulcer, Echinococcosis, Taeniasis/Cysticercosis, Lymphatic Filariasis and Onchocerciasis). Also, review the development of new guanidine derivatives in Malaria and Tuberculosis.

Propargylic alcohols with aryl/heteroaryl groups at C1 position have received significant attention as alkylating agents in direct nucleophilic SN1-type reactions towards the formation of new C-C, C-O, C-N and C-S bonds. Taking advantage of the versatile alkyne functionality, the obtained propargylated derivatives have been transformed into various types of heterocycles as well as carbocycles. This review demonstrates the efficacy and versatility of 1-aryl propargylic alcohols in the synthesis of 5- and 6-membered heterocycles and carbocycles.

Continuing our research programme to develop the synthesis of small heterocyclic entities, in the present study we prepared carbohydrazides of privileged coumarins through highly attractive Meerwein arylation. The reaction condition is compatible with a wide variety of functional groups present on coumarin and aniline, delivered in moderate to good yields of the target scaffolds. The heterocyclic hydrazide skeletons are challenging to synthesize and have tremendous applications in the drug discovery area. The resulting structural diversity was screened for its antitubercular activity utilizing Mtb H37Rv strains via the MABA assay method. The growth inhibition of the designed diversity was found to be in the range 50–97%. Several molecules were found to be promising for further chemical development and in silico analysis.

Polycarbonate (PC)-ZnO NPs composites have been successfully fabricated by solution casting technique in which ZnO NPs (45nm) were prepared via wet chemical method and used as dopant with different concentrations. These nanocomposites were characterized by XRD, SEM, optical micrographs, UV/VIS and FT-IR spectrum. ZnO NPs were uniformly distributed within the PC and create a new recyclable (10 times) catalytic system for the synthesis of α , β-unsaturated compounds and aldimines. Catalytic activity of the nanocomposites increased with ZnO NPs (5%) in PC matrix while at higher loading (9%) slight agglomeration of nanoparticles occurred, which hindered the catalytic effect of nanocomposite.

A new class of amphiphilic triazolyl peptides was designed and synthesized from peptide-based building blocks containing alkyne and azide functional groups namely linear (W(pG))3, cyclic[W(pG)]3, and Ac-K(N3)R-NH2,where W, R, K, and pG represent tryptophan, arginine, lysine, and propargylglycine residues, respectively. The linear (W(pG))3 and cyclic [W(pG)]3 peptides containing alkyne residues were conjugated with Ac-K(N3)R-NH2 functionalized with azide group through click chemistry in the presence of CuSO4.5H2O, Cu (powder), sodium ascorbate, and N,N-disopropylethylamine in methanol:water to afford amphiphilic triazolyl linear-linear (WG(triazole-KR-NH2))3 and cyclic-linear [WG(triazole-KR-NH2)]3 peptides, respectively. The secondary structures of both peptides were similar to a distorted α-helix as shown by CD spectroscopy. TEM imaging showed that linear-linear (WG(triazole-KR-NH2))3 and cyclic-linear [WG(triazole-KR-NH2)]3 peptides formed nano-sized structures in the size range of 50-100 nm and 50-80 nm, respectively.