Advances in chemotherapy of malaria

Saxena, Anil Kumar; Saxena, Mridula

doi:10.1007/978-3-0348-9311-4_8

Cited by 6 publications

(15 citation statements)

References 226 publications

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“…Anal. C, H. The UV and NMR spectra were identical with those reported by Bucourt et al 67a-(ll-Chloroundecyl)estra-l,3,5(10)-triene-3,17j9-diol (3). To the triol 2 (80 mg, 0.18 mmol) was added triphenylphosphine (94 mg, 0.36 mmol) in dry carbon tetrachloride (3 mL), dry THF (0.4 mL), and dry acetonitrile (0.8 mL).…”

Section: Methodssupporting

confidence: 83%

“…The organic phase was dried over magnesium sulfate, filtered, and evaporated to dryness. The iodo derivative 6 was purified by preparative HPLC (MeOH/H20 90:10, tR = 44 min) and crystallized from ether as a white powder (24 mg, 75%): mp 65-66 °C; TLC, £,0.53; UV (EtOH) 281, 287 min; NMR (CDClg) 0.78 (s, 3 H, I8-CH3), 0.99-2.35 (br m, 32 H, chain and steroid), 2.67-2.91 (m, 2 H, 6-CH2), 3.18 (t, 2 H, J = 7.0 Hz, CH2I), 3.75 (t, lH,</= 8.2 Hz, 17-H), 4.62 (s, 1 H, ArOH), 6.55 (d, 1 H, J = 2.8 Hz, 4-H), 6.63 (dd, 1 H, J = 8.4, 2.9 Hz, 2-H), 7.15 (d, 1 H, J = 8.5 Hz, 1-H); MS m/z 552 (27, M+), 424 (1), 271 (1), 253 (15), 171 (22), 157 (100), 145 (47). Anal.…”

Section: Methodsmentioning

confidence: 99%

“…Figure 1. Competitive binding assay of estradiol derivatives (A) 2 ( ), 7 (v), 4 (a), and 8 (O); and (B) 16a-iodoestradiol (as an internal standard) ( ), 5 ( ), 3 (O), 6 ( ), 9 ( ), and unlabeled 17/?-estradiol (•) for calf uterine estrogen receptor labeled with 17/?-[3H]estradiol (incubation for 20 h at 4 °C in the presence of 7% DMF). The concentration required for 50% competition was used to calculate RBA values (see Table I).…”

mentioning

confidence: 99%

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Synthesis and structure-affinity of a series of 7.alpha.-undecylestradiol derivatives: a potential vector for therapy and imaging of estrogen-receptor-positive cancers

Jn¹,

Je²

1990

J. Med. Chem.

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A series of 7 alpha-undecylestradiol derivatives, featuring various substituents at the end of the undecyl spacer chain, were synthesized and evaluated for their interaction with the estrogen receptor and nonreceptor sites. Their relative binding affinities (RBA) for calf uterine estrogen receptors were measured by competitive binding assays and varied between 0.5 and 8.4% of that of unlabeled 17 beta-estradiol. Enhanced lipophilicity and steric hindrance of the substituent on the end of the spacer chain resulted in decreased binding affinity for the estrogen receptor, while interactions with nonreceptor sites increased. RBA values were not affected by prolonged incubation times, suggesting a stable ligand-receptor complex. The potential to use the 7 alpha-undecylestradiol as a vector for site-selective delivery of diagnostic and therapeutic moieties to estrogen-receptor-positive human cancers is discussed.

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Section: Methodssupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Synthesis and structure-affinity of a series of 7.alpha.-undecylestradiol derivatives: a potential vector for therapy and imaging of estrogen-receptor-positive cancers

Jn¹,

Je²

1990

J. Med. Chem.

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“…The enzyme is an important target for medicinal chemistry (5), and inhibitors for it have been used in anticancer (methotrexate [4]), antibacterial (trimethoprim [9]), and antimalarial (pyrimethamine [24]) chemotherapy. DHFR is present in all cells and is necessary for the maintenance of intracellular folate pools in a biochemically active reduced state (18).…”

mentioning

confidence: 99%

Antimycobacterial Activities of 2,4-Diamino-5-Deazapteridine Derivatives and Effects on Mycobacterial Dihydrofolate Reductase

Suling¹,

Seitz

Pathak

et al. 2000

Antimicrob Agents Chemother

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Development of new antimycobacterial agents for Mycobacterium avium complex (MAC) infections is important particularly for persons coinfected with human immunodeficiency virus. The objectives of this study were to evaluate the in vitro activity of 2,4-diamino-5-methyl-5-deazapteridines (DMDPs) against MAC and to assess their activities against MAC dihydrofolate reductase recombinant enzyme (rDHFR). Seventy-seven DMDP derivatives were evaluated initially for in vitro activity against one to three strains of MAC (NJ168, NJ211, and/or NJ3404). MICs were determined with 10-fold dilutions of drug and a colorimetric (Alamar Blue) microdilution broth assay. MAC rDHFR 50% inhibitory concentrations versus those of human rDHFR were also determined. Substitutions at position 5 of the pteridine moiety included ™CH 3 , ™CH 2 CH 3 , and ™CH 2 OCH 3 groups. Additionally, different substituted and unsubstituted aryl groups were linked at position 6 through a two-atom bridge of either ™CH 2 NH, ™CH 2 N(CH 3 ), ™CH 2 CH 2 , or ™CH 2 S. All but 4 of the 77 derivatives were active against MAC NJ168 at concentrations of <13 g/ml. Depending on the MAC strain used, 81 to 87% had MICs of <1.3 g/ml. Twenty-one derivatives were >100-fold more active against MAC rDHFR than against human rDHFR. In general, selectivity was dependent on the composition of the two-atom bridge at position 6 and the attached aryl group with substitutions at the 2 and 5 positions on the phenyl ring. Using this assessment, a rational synthetic approach was implemented that resulted in a DMDP derivative that had significant intracellular activity against a MAC-infected Mono Mac 6 monocytic cell line. These results demonstrate that it is possible to synthesize pteridine derivatives that have selective activity against MAC.

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“…The most currently used antimalarials are potent blood schizontocidals; that is, they act rapidly against the parasite forms that invade erythrocytes and cause the well‐described malaria symptoms. Among the plethora of antimalarial drugs, 8‐aminoquinolines are the most potent class of antimalarial drugs with radical curative activity, having properties to eliminate the hypnozoites from the liver [6]. Considering the historical perspective of aminoquinolines, 8‐aminoquinolines are the successor of quinine ( 1 ) and methylene blue ( 2 ) (Figure ) .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

et al. 2017

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Primaquine (PQ) is the only drug used to prevent relapse of malaria due to P. vivax and P. ovale, by eradicating the dormant liver form of the parasite (hypnozoites). The side-effects associated with PQ limits is uses in treatment of malaria. To overcome the premature oxidative deamination and to increase the life span of drug in the biological system, the novel glyco-conjugates of PQ were synthesized by coupling of primaquine with hexoses in phosphate buffer. The saccharide part of the hybrid molecules thought to direct the drug to the liver, where hypnozoites resides. All the synthesized compounds were fully characterized and evaluated for their radical curative activities. The three compounds viz glucoside (15a), galactoside (15b) and mannoside (15c) with high activity were tested for their activity in rhesus monkeys where the most active compound 15b showed twofold activity (100% radical curative activity at 1.92 mmol/kg) than the standard drug PQ diphosphate (3.861 mmol/kg). It is proposed that results from these studies may be advantageous to develop a new potent tissue schizonticide antimalarial compound.

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Advances in chemotherapy of malaria

Cited by 6 publications

References 226 publications

Synthesis and structure-affinity of a series of 7.alpha.-undecylestradiol derivatives: a potential vector for therapy and imaging of estrogen-receptor-positive cancers

Synthesis and structure-affinity of a series of 7.alpha.-undecylestradiol derivatives: a potential vector for therapy and imaging of estrogen-receptor-positive cancers

Antimycobacterial Activities of 2,4-Diamino-5-Deazapteridine Derivatives and Effects on Mycobacterial Dihydrofolate Reductase

Synthesis of primaquine glyco‐conjugates as potential tissue schizontocidal antimalarial agents

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