Several derivatives of aminobenzoboroxole have been prepared starting from 2-boronobenzaldehyde. All of these derivatives have been evaluated for their anti-mycobacterial activity on Mycobacterium smegmatis and cytotoxicity on breast cancer cell line MCF7. Based on these studies, all the tested molecules have been found to be generally non-toxic and benzoboroxoles with unsubstituted (primary) amines have been found to exhibit good anti-mycobacterial activity. Some of the key compounds have been evaluated for their anti-tubercular activity on Mycobacterium tuberculosis H37Rv using 7H9 and GAST media. 7-Bromo-6-aminobenzoboroxole 4 has been identified as the lead candidate compound for further development.

Novel N,N-dialkyl carboxy coumarins have been synthesized as potential anticancer agents via inhibition of monocarboxylate transporter 1 (MCT1). These coumarin carboxylic acids have been evaluated for their in vitro MCT1 inhibition, MTT cancer cell viability, bidirectional Caco-2 cell permeability, and stability in human and liver microsomes. These results indicate that one of the lead candidate compounds 4a has good absorption, metabolic stability, and a low drug efflux ratio. Systemic toxicity studies with lead compound 4a in healthy mice demonstrate that this inhibitor is well tolerated based on zero animal mortality and normal body weight gains compared to the control group. In vivo tumor growth inhibition studies in mice show that the candidate compound 4a exhibits significant single agent activity in MCT1 expressing GL261-luc2 syngraft model but doesn’t show significant activity in MCT4 expressing MDA-MB-231 xenograft model, indicating the selectivity of 4a for MCT1 expressing tumors.

Potent monocarboxylate transporter 1 inhibitors (MCT1) have been developed based on α-cyano-4-hydroxycinnamic acid template. Structure–activity relationship studies demonstrate that the introduction of p-N, N-dialkyl/diaryl, and o-methoxy groups into cyanocinnamic acid has maximal MCT1 inhibitory activity. Systemic toxicity studies in healthy ICR mice with few potent MCT1 inhibitors indicate normal body weight gains in treated animals. In vivo tumor growth inhibition studies in colorectal adenocarcinoma (WiDr cell line) in nude mice xenograft models establish that compound 27 exhibits single agent activity in inhibiting the tumor growth.Keywords: colorectal adenocarcinoma; monocarboxylate transporter 1; reverse Warburg effect; Warburg effect; α-cyano-4-hydroxycinnamic acid

Novel functionalized quaternary ammonium curcuminoids have been synthesized from piperazinyl curcuminoids and Baylis–Hillman reaction derived allyl bromides. These molecules are found to be highly water soluble with increased cytotoxicity compared to native curcumin against three cancer cell lines MIAPaCa-2, MDA-MB-231, and 4T1. Preliminary in vivo toxicity evaluation of a representative curcuminoid 5a in healthy mice indicates that this molecule is well tolerated based on normal body weight gains compared to control group. Furthermore, the efficacy of 5a has been tested in a pancreatic cancer xenograft model of MIAPaCa-2 and has been found to exhibit good tumor growth inhibition as a single agent and also in combination with clinical pancreatic cancer drug gemcitabine.

Alkylation of amino-acid derived iminoesters with Baylis–Hillman (BH) template based allyl bromides furnished α-methylene-β-substituted-pyroglutamates, while the corresponding alkylation with BH derived allylic acetates provided α-alkylidene-pyroglutamates. These methodologies have been applied in the synthesis of fused [3.2.0]-γ-lactam-β-lactones.

Novel stereoselective synthesis of α-methylene-β-substituted pyroglutamates, and α-alkylidene-pyroglutamates has been achieved via substrate controlled asymmetric alkylation of l-threonine derived oxazole with Baylis–Hillman reaction based allyl bromides and acetates, respectively. The synthesized compounds were evaluated for their proteasome inhibition and cytotoxicity on multiple myeloma cells.Novel stereoselective synthesis of α-methylene-β-substituted pyroglutamates, and α-alkylidene-pyroglutamates has been achieved via substrate controlled asymmetric alkylation of l-threonine derived oxazoles with Baylis–Hillman reaction based allyl bromides and acetates, respectively.

An efficient methodology for the preparation of α-hydroxyamides via boric acid-mediated addition of isonitriles onto aldehydes has been developed. The reaction of isonitriles with α-boronobenzaldehyde takes place under intramolecular catalysis conditions to provide functionalized benzoxaboroles.An efficient methodology for the preparation of α-hydroxyamides via boric acid-mediated addition of isonitriles on to aldehydes has been developed. The reaction of isonitriles with α-boronobenzaldehyde takes place under intramolecular catalysis conditions to provide functionalized benzoxaboroles.

2-Formylphenylboronic acids upon reaction with activated olefins such as acrylates, methyl vinyl ketone, and acrylonitrile provide functionalized benzoboroxoles. The corresponding homologated benzoboroxoles were synthesized via the reaction of 2-formylphenylboronic acids with α-bromomethylacrylates.2-Formylphenylboronic acids upon reaction with activated olefins such as acrylates, methyl vinyl ketone, and acrylonitrile provide functionalized benzoboroxoles. The corresponding homologated benzoboroxoles were synthesized via the reaction of 2-formylphenylboronic acids with α-bromomethylacrylates.

A short protocol for the practical scale synthesis of several ω-borono-α-amino acids is described via the alkylation of benzophenone glycinimines with various electrophiles.

The reaction of carboxylic acids with Baylis-Hillman reaction derived α-bromomethyl acrylic esters readily provide 2-(alkoxycarbonyl)allyl esters in good to excellent yields. These functionalized allyl esters have been evaluated for their cell proliferation inhibition properties against breast cancer (MDA-MB-231 and 4T1) and pancreatic cancer (MIAPaCa-2) cell lines to explore their potential as anticancer agents. Several of the synthesized derivatives exhibit good potency against all three cancer cell lines. Our structure activity relationship (SAR) studies on 2-carboxycarbonyl allyl esters indicate that substituted aromatic carboxylic acids provide enhanced activity compared to substituted aliphatic carboxylic acid analogs. Di- and tri-allyl esters derived from di-and tri-carboxylic acids exhibit higher inhibition of cell proliferation than mono esters. Further SAR studies indicate that the double bond in the 2-(alkoxycarbonyl)allyl ester is required for its activity, and there is no increase in activity with increased chain length of the alkoxy group. Two lead candidate compounds have been identified from the cell proliferation inhibition studies and their preliminary mechanism of action as DNA damaging agents has been evaluated using epifluorescence and western blot analysis. One of the lead compounds has been further evaluated for its systemic toxicity in healthy CD-1 mice followed by anticancer efficacy in a triple negative breast cancer MDA-MB-231 xenograft model in NOD-SCID mice. These two in vivo studies indicate that the lead compound is well tolerated in healthy CD-1 mice and exhibits good tumor growth inhibition compared to breast cancer drug doxorubicin.

A short protocol for the practical scale synthesis of several ω-borono-α-amino acids is described via the alkylation of benzophenone glycinimines with various electrophiles.

Alkylation of amino-acid derived iminoesters with Baylis–Hillman (BH) template based allyl bromides furnished α-methylene-β-substituted-pyroglutamates, while the corresponding alkylation with BH derived allylic acetates provided α-alkylidene-pyroglutamates. These methodologies have been applied in the synthesis of fused [3.2.0]-γ-lactam-β-lactones.