Mohsen Daneshtalab

Chlorogenic Acid Derivatives with Alkyl Chains of Different Lengths and Orientations: Potent α-Glucosidase Inhibitors

Alpha-glucosidases play important roles in the digestion of carbohydrates and biosynthesis of viral envelope glycoproteins. Inhibitors of alpha-glucosidase are promising candidates for the development of antitype II diabetics and anti-AIDS drugs. Here, we report the synthesis and alpha-glucosidase inhibitory activity of mono- and diketal/acetal derivatives of chlorogenic acid. The diketal derivatives showed more potent inhibitory activity than the monoketals. The 1,7-(5-nonanone) 3,4-(5-nonanone)-chlorogenic acid diketal showed remarkable inhibitory activity against alpha-glucosidases with potency better than that of 1-deoxynojirimycin hydrochloride. Four diasteremers of pelargonaldehyde diacetal and two of monoacetal derivatives of chlorogenic acid were synthesized in this study. They showed significant potent inhibition similar to or more potent than the ketal counterparts. Acetals with the alkyl chain oriented toward position 2 of chlorogenic acid showed more potent activity than those oriented toward position 6.

Synthesis, anti-fungal and 1,3-β-D-glucan synthase inhibitory activities of caffeic and quinic acid derivatives

New derivatives of caffeic acid and quinic acid were synthesized and their anti-fungal and inhibitory activities on fungal 1,3-β-glucan synthase were determined in comparison with those of the corresponding chlorogenic acid derivatives. All the chlorogenic, quinic and caffeic acid derivatives that were coupled with an H(2)N-orn-4-(octyloxy) aniline group (1, 1b and 1c) displayed potent activities in both anti-fungal and inhibition of 1,3-glucan synthase assays. Compounds 1 and 1c inhibited the fungal membrane enzyme with the potency comparable to that of a known 1,3-β-D-glucan synthase inhibitor, aculeacin A. The results revealed that the anti-fungal activity of the chlorogenic acid derivative with a free amino group was at least partly due to inhibition of the fungal 1,3-β-glucan synthase. These results suggest that further investigation on caffeic acid derivatives may lead to the discovery of novel anti-fungal agents with drug-like properties.

Synthesis, anti-HIV and anti-oxidant activities of caffeoyl 5,6-anhydroquinic acid derivatives

In our continued research on chlorogenic acid analogues and derivatives with improved bioactivity, we have synthesized some caffeoyl 5,6-anhydroquinic acid derivatives. The 1,7 acetonides of chlorogenic acid (15), and of the mono-caffeoyl 5,6-anhydroquinic acids (7-8) showed appreciable anti-HIV activity. The 3,4-dicaffeoyl 5,6-anhydroquinic acid (12) exhibited an anti-HIV activity twice as that of 3,5-dicaffeoylquinic acid (22). The caffeoyl 5,6-anhydroquinic acid derivatives displayed potent anti-oxidant activities. The mono-caffeoyl 5,6-anhydroquinic acids (10-11) were more than twice stronger than chlorogenic acid (21) on SOD-like activity.

Discovery of Chlorogenic Acid-Based Peptidomimetics as a Novel Class of Antifungals. A Success Story in Rational Drug Design

Life-threatening fungal infections have increased dramatically in recent decades in immunocompromised patients. An estimated 40% of all deaths from hospital-acquired infections are due to infections caused by opportunistic fungi. The current treatment options are either causing serious toxicity, or becoming inactive against the drug-resistant fungal strains. Thus, the discovery and development of new antifungal agents that are economically feasible, have excellent therapeutic value, and address the problems of toxicity and species resistance is very important. We have recently designed and synthesized a series of chlorogenic acid-based peptidimimetics using structure-based methodology starting with cyclic peptides of the candin class of antifungals. These novel and totally synthetic compounds exhibit promising antifungal activity against pathogenic fungi with very low toxicity against brine shrimps. The possible novelty in their mechanism of action and economically feasible synthetic approach are the attractive features of this class of compounds that make them different from the already utilized antifungal agents.

In Vitro antifungal activity of 2-(4-substituted phenyl)-3(2H)-isothiazolones

Thein vitro antifungal activity of several N2-phenyl-3(2H)-isothiazolones substituted at C4 of the phenyl moiety with heterocyclic nucleus or groups of different physico-chemical properties against four human pathogenic fungi was determined by broth macrodilution method; results were compared with those obtained with itraconazole and ketoconazole. These isothiazolones showed moderate to high activity against some or all tested strains and in comparison with the reference drugs, 5-chloro-2-(4-nitrophenyl)isothiazol-3-one (1g), 5-chloro-2-phenylisothiazol-3-one (1c), 4-[4-(5-chloro-3-oxo-3H-isothiazol-2-yl)phenyl]-1,4-dihydrotriazol-5-one (1s) and 2-(4-nitrophenyl)isothiazol-3-one (2g) againstAspergillus niger, 5-chloro-2-(4-nitrophenyl)isothiazol-3-one (1g) and 4-[4-(5-chloro-3-oxo-3H-isothiazol-2-yl)phenyl]piperazine-1-carboxamide (1q) againstTrichophyton mentagrophytes had comparable activity, compounds1g and2g showing higher activity againstMicrosporum canis. Antifungal activity was favored by the presence of chlorine at C5 of the isothiazolone and/or the presence of nitro group or heterocyclic nucleus at C4 of the phenyl ring and proper hydrophilicity of the molecule.

Novel catalytic synthesis of 6,7-dimethoxyisatin with the use of heteropolyacids (HPAs) as acid solid catalyst

Novel catalytic synthesis of 6,7-dimethoxyisatin with the use of heteropolyacids (HPAs) as acid solid catalyst An efficient method for the preparation of 6,7-dimethoxyisatin and its derivatives was developed with good yield by using Preyssler-type heteropolyacid (HPA) as acid catalyst under green conditions. The comparison between Keggin type heteropolyacids, H3[PW12O40], H4[SiW12O40] and H4[SiMo12O40], H3[PMo12O40] and mineral acids with Preysslers anion shows that the latter possess better catalytical activity than the other heteropolyacids and no degradation of the structure was observed.

One-pot synthesis of (S)-2-(6-methoxynaphtalen-2-yl)propanoic acid, (S)-Naproxen using Preyssler and Keggin-type heteropolyacids as green and reusable catalysts

One-pot synthesis of (S)-2-(6-methoxynaphtalen-2-yl)propanoic acid, (S)-Naproxen using Preyssler and Keggin-type heteropolyacids as green and reusable catalysts A simple, clean and environmentally benign route to the enantioselective synthesis of (S)-2-(6-methoxynaphtalen-2-yl)propanoic acid, (S)-Naproxen 3 is described by using Preyssler heteropolyacid, H14[NaP5W30O110], as a green and reusable catalyst in water and in the presence of 1-(6-methoxynaphthalen-2-yl)propan-1-one 1, D-mannitol 2. The products were obtained in very good yields.

4-Oxo-1,4-dihydro-benzo[h][1,3]thia-zeto[3,2-a]quinoline-1,3-dicarb-oxy-lic acid.

In the title molecule, C16H9NO5S, there is an intramolecular O—H⋯O hydrogen bond involving the quinolone carbonyl O atom and a carboxyl OH group. In the crystal, intermolecular O—H⋯O hydrogen bonds between the carbonyl group of the quinolone carboxyl group, and a second carboxyl group on the thiazeto moiety lead to the formation of chains propagating along [201] and perpendicular to the π-stacks of molecules.