Bhuwan B. Mishra

Natural products: an evolving role in future drug discovery.

The therapeutic areas of infectious diseases and oncology have benefited from abundant scaffold diversity in natural products, able to interact with many specific targets within the cell and indeed for many years have been source or inspiration for the majority of FDA approved drugs. The present review describes natural products (NPs), semi-synthetic NPs and NP-derived compounds that have undergone clinical evaluation or registration from 2005 to 2010 by disease area i.e. infectious (bacterial, fungal, parasitic and viral), immunological, cardiovascular, neurological, inflammatory and related diseases and oncology.

Natural product based leads to fight against leishmaniasis

The growing incidence of parasitic resistance against generic pentavalent antimonials, specifically for visceral disease in Indian subcontinent, is a serious issue in Leishmania control. Notwithstanding the two treatment alternatives, that is amphotericin B and miltefosine are being effectively used but their high cost and therapeutic complications limit their use in endemic areas. In the absence of a vaccine candidate, identification, and characterization of novel drugs and targets is a major requirement of leishmanial research. This review describes current drug regimens, putative drug targets, numerous natural products that have shown promising antileishmanial activity alongwith some key issues and strategies for future research to control leishmaniasis worldwide.

Alkaloids: Future prospective to combat leishmaniasis

Leishmaniasis, a vector-borne parasitic disease resulting from infection of macrophages by obligate intracellular parasites of genus Leishmania, has been considered a major tropical disease by the World Health Organization. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions because of its efficacy and cost effectiveness. However, the growing incidence of resistance for the pentavalent antimony complex in endemic and non-endemic regions has seriously hampered their use in these regions. The second line drugs such as amphotericin B, paromomycin and miltefosine are the other alternatives, but they merely fulfill the desired requirements of a safe drug. The recent researches focused on plants have shown a wise way to get a true and potentially rich source of drug candidates against leishmaniasis, where alkaloids have been found more effective. The present review initially highlights the current status of leishmaniasis, synergy of the disease with HIV, therapeutic options available and in later sections summarizes all alkaloids, which have shown significant antileishmanial activities.

Fighting Against Leishmaniasis: Search of Alkaloids as Future True Potential Anti-Leishmanial Agents

Leishmaniasis, a group of tropical diseases caused by protozoan parasites of genus Leishmania, is a major health problem worldwide that affects millions of people especially in the developing nations. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness, but the growing incidence of their resistance has seriously hampered their use. In many cases the drugs employed for the treatment are toxic, marginally effective, given by injection and, compromised by the development of resistance. Therefore, the development of new mechanism based safe, effective and affordable chemotherapeutic agents to fight leishmaniasis would be an urgent priority research. The recent researches focused on natural products have shown a wise way to get a true and potentially rich source of drug candidates against leishmaniasis, where alkaloids have been found more effective. The present review briefly illustrates an account on current status of leishmaniasis, life cycle of parasites and biology, synergy of the disease with HIV, therapeutic options available to cure this disease and, highlights why natural products especially alkaloids as folk medicines are so important? Additionally, the outlines for the leishmanicidal activities of various alkaloids including indole, quinoline, isoquinoline, pyrimidine-beta-carboline, steroidal and diterpene alkaloids from various plants as well as alkaloids from marine sources have been provided with their mechanistic studies.

Diacetoxyiodobenzene mediated one-pot synthesis of diverse carboxamides from aldehydes.

A novel, one-pot, and highly facile protocol has been devised for an easy access of a series of novel glycosyl carboxamides from aldehydes using diacetoxyiodobenzene in the presence of ionic liquid at ambient temperature.

Alkaloids as potential anti-tubercular agents.

An increasing incidence of deaths due to tuberculosis and the known drawbacks of the current existing drugs including the emergence of multi drug-resistant strains have led to a renewed interest in the discovery of new anti-tubercular agents with novel modes of actions. The recent researches focused on natural products have shown a useful way to obtain a potentially rich source of drug candidates, where alkaloids have been found more effective. The present review focuses on current epidemiology of tuberculosis, synergy of the disease with HIV, current therapy, available molecular targets and, highlights why natural products especially alkaloids are so important. The review summarizes alkaloids found active against mycobacteria from the mid-1980s to late 2008 with special attention on the study of structure-activity relationship (SAR).

Synthesis of glycoconjugate benzothiazoles via cleavage of benzotriazole ring.

A concise and efficacious benzotriazole-mediated novel two-step protocol has been developed for easy access to glycoconjugate benzothiazoles from protected carbohydrates. The benzotriazolemethanethione 3, prepared by the reaction of free alcohol with bis(1H-benzo[1,2,3]triazol-1-yl)methanethione, on treatment with silanes or stannane under heating or microwave irradiation undergoes free radical β-scission of N-N bond and affords diverse range of 2-O-substituted benzothiazoles 4 via cyclative elimination of molecular nitrogen. The structures of all of the compounds have been elucidated using IR, NMR, MS, and elemental analysis, and five of them have been characterized by single-crystal X-ray analysis.

Synthesis of 2-N/S/C-substituted benzothiazoles via intramolecular cyclative cleavage of benzotriazole ring.

The synthesis of numerous 2-N/S/C-substituted benzothiazoles was achieved from substituted thiocarbonylbenzotriazoles via free-radical intramolecular cyclative cleavage of the benzotriazole ring in the presence of (TMS)3SiH and AIBN under mild conditions. The developed methodology demonstrates significant compatibility under microwave conditions and is important as it avoids the use of toxic metals for radical cyclization.

Click inspired synthesis of antileishmanial triazolyl O-benzylquercetin glycoconjugates

AbstractThe 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with O-benzylquercetin alkynes (5–7) to afford regioselective triazole-linked O-benzylquercetin glycoconjugates (8–10) was investigated in the presence of CuI/DIPEA in dichloromethane. All the developed glycoconjugates (8–10) were evaluated for anti-leishmanial activity against the promastigotes and amastigotes of Leishmania donovani. Graphical AbstractClick Inspired Synthesis of Antileishmanial Triazolyl O-Benzylquercetin Glycoconjugates

Click chemistry inspired highly facile synthesis of triazolyl ethisterone glycoconjugates.

Numerous deoxy-azido sugars 3 were prepared by the reaction of tosyl/bromo sugars with NaN3 in dry DMF under heating condition. The 1,3-dipolar cycloaddition of deoxy-azido sugars 3 with ethisterone 4 to afford regioselective triazole-linked ethisterone glycoconjugates 5 was investigated in the presence of CuI and DIPEA in dichloromethane or CuSO4·5H2O and sodium ascorbate in aqueous medium. All the developed compounds were characterized by spectroscopic analysis (IR, (1)H &(13)C NMR, and MS spectra). Structure of triazolyl ethisterone glycoconjugate 5a has been further confirmed by its Single Crystal X-ray analysis.