Recent advances in multitarget-directed ligands via in silico drug discovery.

To combat multifactorial refractory diseases, such as cancer, cardiovascular, and neurodegenerative diseases, multitarget drugs have become an emerging area of research aimed at 'synthetic lethality' (SL) relationships associated with drug-resistance mechanisms. In this review, we discuss the in silico design of dual and triple-targeted ligands, strategies by which specific 'warhead' groups are incorporated into a parent compound or scaffold with primary inhibitory activity against one target to develop one small molecule that inhibits two or three molecular targets in an effort to increase potency against multifactorial diseases. We also discuss the analytical exploration of structure-activity relationships (SARs), physicochemical properties, polypharmacology, scaffold feature extraction of US Food and Drug Administration (FDA)-approved multikinase inhibitors (MKIs), and updates regarding the clinical status of dual-targeted chemotypes.

In vitro screening of natural product-based compounds for leishmanicidal activity.

Leishmaniasis is one of the major parasitic diseases, caused by obligate intracellular protozoa having high mortality as well as morbidity rate. As there is no human licensed vaccine available against leishmaniasis, chemotherapy remains the major way of combating this disease. Many disadvantages are known to be associated with the current drug regime including severe side effects and toxicity, long duration and expensive treatment, and the emergence of resistance.

The Mukaiyama type aldol reaction for the synthesis of trans-2,6-disubstituted tetrahydropyrans: synthesis of diospongin A and B.

An efficient synthesis protocol for the preparation of trans-2,6-disubstituted tetrahydropyrans by the reaction of 1-phenyl-1-triemthylsiloxyethylene with six membered cyclic hemiacetals in the presence of iodine is developed. This reaction proceeds smoothly under mild conditions employing a catalytic amount of molecular iodine. The feature of this novel conversion includes milder reaction conditions, broader substrate scope, functional group tolerance and good diastereoselectivity.

Total Synthesis of Four Isomers of the Proposed Structures of Cryptorigidifoliol K.

The first asymmetric convergent total synthesis of four isomers of proposed structures of cryptorigidifoliol K (1a, 1b, 1c, and 1d) has been achieved from commercially available starting materials. The key steps in this synthesis involve tandem isomerization followed by a C-O and C-C bond-forming reaction for the construction of trans-2,6-disubstituted dihydropyran, iodolactonization, isomerization of terminal alkene, and cross-metathesis reaction. The large discrepancies in the spectroscopic data (H NMR) of synthetic cryptorigidifoliol K from the natural product suggest that the structure of the natural cryptorigidifoliol K requires revision.