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Biomedical subjects

S K Sengupta

Publications and source records attributed to S K Sengupta.

At least 37 records · Page 2Linked to original sources
PubMed1989

Seat-belt message and the law?

This paper attempts to draw together available information on the use of seat belts, one of the most important safety devices for a person in a car. Considering the high rate of mortality and morbidity due to road traffic accidents in Papua New Guinea the authors strongly feel that seat-belt usage should be made compulsory. When one looks at the history of the implementation of such a successful countermeasure in other countries it seems that legislation is the only answer.

Attitude↗
PubMed1988

Studies on some iridium(III) complexes with Schiff bases derived from amino carboxylic acids.

The reactions of iridium(III) chloride with different Schiff bases gave complexes of types [Ir(SB)3], [Ir(SB')Cl(H2O)2], [Ir(SB'')Cl2]n, [Ir(SB'' ')Cl(H2O)]n (SBH = Schiff bases derived from anthranilic acid and benzaldehyde, acetophenone, vanillin, cinnamaldehyde or m-hydroxyacetophenone; SB'H2 = Schiff bases derived from anthranilic acid and salicylaldehyde or o-hydroxyacetophenone; SB''H = Schiff bases derived from p-aminobenzoic acid and benzaldehyde, acetophenone, vanillin, cinnamaldehyde, or m-hydroxyacetophenone; SB'' 'H2 = Schiff bases derived from p-aminobenzoic acid and salicylaldehyde or o-hydroxyacetophenone). These complexes have been characterized on the basis of elemental analyses, conductance, magnetic moment, and spectral (electronic, i.r., and 1H n.m.r.) data. The electronic spectra reveals octahedral geometry for these complexes except for [Ir(SB'')Cl2]n, which is trigonal bipyramidal. The thermal behavior of these complexes has also been studied by TG, DTG, and DSC techniques. The different kinetic parameters, viz., order of reaction, activation of energy, and heat of reaction were calculated. The antifungal and antiviral activities of the complexes with Schiff bases derived from anthranilic acid have also been investigated.

4-Aminobenzoic Acid↗
PubMed1988

New actinomycin D analogues as superior chemotherapeutic agents against primary and advanced colon tumors and colon xenografts in nude mice.

"Reverse" analogues (RAD's) of actinomycin D (AMD) and their antitumor activity against mouse and human colon tumor cells are reported. RAD's are tetracyclic, and they have an oxazole ring fused on the tricyclic phenoxazine chromophore of AMD. The oxazole ring in RAD is substituted at the C-2 carbon with either a CH3 (in RAD I), a C6H5 (in RAD II), or a CH2CONH(CH2)4NH2 (in RAD III) group. In tumor cells and rat hepatic microsomes, RAD's are metabolized to a tricyclic "symmetrical" analogue of AMD (SAD) with the loss of the oxazole ring and its substituents. RAD and SAD are very active in priming superoxides in the presence of microsomal enzymes as well as in inhibiting the synthesis of DNA and the growth of human colon tumor HT-29 cells in vitro. RAD III and SAD efficiently cleave closed circular plasmid pBR322 DNA like the antitumor agent bleomycin. In addition to their strong inhibitory activity against P388 and B16 tumors in vitro and in vivo, RAD III and SAD demonstrate high levels of activity against primary C26 and advanced C38 colon tumors in mice and against a xenograft of human colon adenocarcinoma CX-1 in athymic mice. In all these biological activities, the analogues demonstrate superiority to AMD in several experimental tumors. Also, the analogues, in contrast to AMD, show reduced toxicity in tumor-free mice, which is possibly due to the metabolic deactivation of SAD in host organs.

Animals↗
PubMed1988

Synthesis and biological properties of actinomycin D chromophoric analogues substituted at carbon 7 with aziridine and cyclopropyl functions.

The growing importance of functionalized tricyclic rings, e.g., cyclopropyl and aziridine, in numerous organic biomolecules led us to develop syntheses of novel actinomycin D (AMD) analogues substituted with aziridine and cyclopropyl functions. Reaction of 7-hydroxyactinomycin D with 1-aziridineethyl iodide and bromomethylcycloporopane afforded the desired 7-[2-(1-aziridinyl)ethoxy] and cyclopropylmethoxy analogues, respectively. Calf thymus DNA binding of these analogues was comparable to that of AMD as examined by UV-vis difference spectral measurements, CD techniques, and relaxation of supercoiled closed circular SV40 DNA, indicating an intercalative mode of binding to the DNA duplex. Thermal denaturation of DNA experiments employing higher temperatures than room temperature exhibit a thermal lability of the DNA analogue complexes, suggestive of a probable covalent bond formation with DNA bases. The analogues were found to be 1/4-1/40 as cytotoxic to human lymphoblastic CCRF-CEM leukemia and B16 melanoma cells in vitro as AMD, with ID50 values in the nanomolar concentration range.

Aziridines↗
PubMed1988

Enantiomers of 7-(2,3-epoxypropoxy)actinomycin D as dual-action DNA-acting antitumor agents.

Enantiomeric forms of (+/-)-EPA [racemic 7-(2,3-epoxypropoxy)actinomycin D] have been synthesized; these are (R)-(+)- and (S)-(-)-EPA, which are active against a range of actinomycin resistant and marginally responsive tumors. The R-(+) enantiomer is uniformly superior to the other forms in all the tumor lines tested. These enantiomers act by binding to DNA, both by intercalation and alkylation at the guanine base of DNA. They are superior to actinomycin D in their in vitro activity against mouse leukemias (L1210 and P388/ADR) and mouse melanoma B16. This superior activity is also evident against all the preceding mouse leukemias and against solid tumors B16 and C26 in vivo. In biochemical action, the enantiomers behave similarly and act primarily by inhibiting DNA synthesis in tumor cells; the only difference found was in their preference for sites in DNA bases during alkylation. The R-(+) enantiomer generates an adduct that is believed to be bonded to the N7-site of guanosine; conversely, the S-(-) isomer forms two adducts with DNA that are different from the preceding one by HPLC and are tentatively assigned O6-guanosine-substituted structures on the basis of their UV, CD, and other chemical behaviors.

Animals↗
PubMed1988

Childhood malignant tumours in Papua New Guinea.

Data from the Papua New Guinea Tumour Registry and the Central Pathology Department were reviewed in order to document the incidence and pattern of malignancies in children in Papua New Guinea. Altogether, 680 cases of histologically defined childhood malignancies were recorded during the 14.5 years from 1971 to 1985. The frequencies of the various tumours were compared with past data and with published data from other countries. The incidence of malignancies in Papua New Guinean children appeared to be low, 36.5/1,000,000/year, with a male:female ratio of 1.6:1. Lymphoma was the most commonly occurring tumour and Burkitt's tumour accounted for 53% in this group. The relative frequency of leukaemia compared with lymphoma appeared to have increased since a previous report. A relatively high incidence of retinoblastoma (6.9%) and of other embryonal tumours (4.8%) was recorded, whilst the recorded incidences of tumours of the central nervous system (3.8%) and neuroblastoma (3.7%) were low. Ewing's sarcoma accounted for almost half of the bone tumours, whilst Kaposi's sarcoma was a relatively frequent soft tissue tumour. Differences and similarities between the Papua New Guinea data and those from other countries are discussed.

Adolescent↗
PubMed1988

Fibrocalculous pancreatic diabetes in Papua New Guinea.

Fibrocalculous pancreatic diabetes of the tropics has not been previously identified in Papua New Guinea where the prevalence of Type 2 (non-insulin-dependent) diabetes is increasing. Four patients with this syndrome:--onset of diabetes before the age of 30 years, low body mass index, radiologic pancreatic calcification and marked hyperglycaemia with resistance to ketosis were recognized over three years at Port Moresby General Hospital. Two patients had a history of recurrent abdominal pain in childhood, and two patients had documented insulin requirement greater than 1.5 U/kg daily, and insulin resistance confirmed by intravenous insulin tolerance test. Plasma C-peptide was present in the three cases tested. In the two patients tested islet cell antibodies were not detected but in both there was a prominent diffuse acinar stain suggestive of antibodies to acinar tissue.

Adolescent↗
PubMed1987

Synthesis and biological properties of actinomycin D chromophoric analogues substituted at the 7-carbon with aziridine and aminopropoxy functions.

The growing importance of functionalized aziridines in numerous organic biomolecules led us to develop syntheses of novel actinomycin D (AMD) analogues substituted with an aziridine. Reaction of 7-hydroxyactinomycin D with 2-(iodomethyl)aziridine produced the desired 7-(2-aziridinylmethoxy)actinomycin analogue. In an attempt to develop an alternate route to this analogue, 7-(2-azido-3-iodopropoxy)actinomycin was subjected to reduction with dimethylamine-borane complex; the reaction did not produce the three-membered aziridine; instead the reaction product was found to be linear 7-(2-aminopropoxy)actinomycin D. Calf-thymus-DNA binding of these analogues was comparable to that of AMD as examined by UV-visible difference spectral measurements, thermal denaturation of DNA, and CD techniques. The analogues were found to be about 1/4 to 1/30 as cytotoxic to human lymphoblastic CCRF-CEM leukemia and B16 melanoma cells in vitro as AMD.

Cell Line↗
PubMed1987

Ovarian neoplasms in children and adolescents in Papua New Guinea.

A study of ovarian tumours in young females under the age of 20 years in Papua New Guinea between the period 1976-1986 is presented. During these 11 years a total of 101 cases was seen among 802 ovarian tumours reported in all age groups. Epithelial tumours comprised the largest number (66.3%) followed by germ cell tumours (24.8%). Ten patients (9.9%) presented with torsion. Only 3 (3%) cases of Burkitt lymphoma were recorded (3%); the series included 1 case of primary non-gestational choriocarcinoma of the ovary in an 11-year-old premenarchal girl.

Adolescent↗
PubMed1986

Childhood Kaposi's sarcoma in Papua New Guinea.

In the country of Papua New Guinea, with its diverse population of nearly 3 million people, some disease patterns have a strange similarity to those seen in tropical Africa. Kaposi's sarcoma is a condition which is commonly seen in adult males; childhood Kaposi's sarcoma is relatively uncommon. Six cases, all males, aged from 6 months to 12 years have been detected since 1978. The primary organ involvement included skin in four cases, oral cavity in one case and lymph node in one case. The varied clinico-pathological features are described. This is the first report of such cases from Papua New Guinea.

Child, Preschool↗
PubMed1986

DNA-binding abilities of bisguanylhydrazones of anthracene-9,10-dicarboxaldehyde.

DNA-binding strengths of three anthracene-9,10-dicarboxaldehyde hydrazones were examined by spectral shifts of the drug-DNA combinations, spectral titration by Scatchard plots, elevation of DNA melting temperature during complexation and comparison of spectral shifts in the presence of DNA's having variable base contents. Dissociation of the DNA-complexes was also observed. The results showed a strong degree of binding by the three compounds. They did not exhibit noticeable base-pair specificity, but both associated with and dissociated rapidly from DNA. Scatchard plots for DNA association indicated two types of binding; the stronger was most likely due to intercalation of the planar anthracene ring into the DNA double helix. No direct correlation can be drawn between the observed anti-cancer activities and DNA binding affinities of these compounds in vitro.

Anthracenes↗
PubMed1985

"Reverse" and "symmetrical" analogues of actinomycin D: metabolic activation and in vitro and in vivo tumor growth inhibitory activities.

Two new classes of actinomycin D analogues, tetracyclic "reverse" analogues and a tricyclic "symmetrical" analogue of actinomycin D, are reported. These analogues bind to DNA and the binding does not occur by an intercalation mechanism. The analogues inhibit the synthesis of DNA and RNA in P388 tumor cells and the growth of CCRF-CEM cells in vitro at nanomolar concentrations. The tetracyclic "reverse" analogues, which are structurally related to the previously reported actinomycin D oxazolyl analogues, are metabolized in the presence of rat hepatic microsomes and tumor cell homogenates. The metabolism takes place with the loss of the oxazole ring; thus the "reverse" analogues produce a major metabolite which is the "symmetrical" analogue; the actinomycin oxazolyl analogues generate 7-hydroxyactinomycin D. Further, the microsomes activate the analogues to free-radical states which catalyze the production of superoxide as shown by stimulation of epinephrine oxidation and also indicated by electron paramagnetic resonance studies. The "symmetrical" and "reverse" analogues also demonstrate very high activities in these systems. In in vivo studies using P388/S, P388/ADR leukemia, and B16 melanoma in mice, the analogues showed increased activity and superior therapeutic index values, in comparison to actinomycin D.

Animals↗
PubMed1985

Enzymic and chemical reduction of 2-deaminoactinomycins to free radicals.

The antitumour activity of actinomycin D (AMD) has been proposed to result, in part, from its intercalation into DNA dG-dC base-pairs leading to an inhibition of RNA synthesis. We have recently prepared 2-deamino-2-nitroactinomycin D and 2-deamino-actinomycin D and determined that, unlike AMD, these analogues do not intercalate into calf-thymus DNA. In the present study we show that these analogues and their corresponding peptide-free diethylamino derivatives are more effective than the parent AMD in forming ion radicals, in stimulating oxygen uptake and in forming superoxide anion when incubated in the presence of NADPH and NADPH cytochrome P-450 reductase. NaBH4-mediated reduction of these compounds yielded free radicals as shown by electron paramagnetic resonance (e.p.r.) spectroscopy. Free radicals could also be generated by incubation of these actinomycins with NADPH and either liver microsomes or purified NADPH cytochrome P-450 reductase. In the presence of molecular oxygen these free radicals spontaneously reoxidized by transfer of a single electron to molecular oxygen to form superoxide. Relative rates of superoxide formation were established for these substrates with the 2-deamino-2-nitroactinomycin D exhibiting the highest activity. It is proposed that the antitumour activity of these AMD analogues results, in part, from their ability to form reactive reduced oxygen species and, as such, these actinomycin derivatives may serve as useful probes for the tumouricidal mechanism of this family of agents.

Dactinomycin↗
PubMed1984

Differences in physical and biological properties of 50S ribosomes and 23S RNAs derived from tight and loose couple 70S ribosomes.

Tight couple (TC) 50S ribosomes on treatment with kethoxal lose their capacity to associate with 30S ribosomes whereas loose couple (LC) 50S ribosomes on such treatment fully retain their association capacity. The same is true for 23S RNAs isolated from treated 50S ribosomes or isolated 23S RNAs directly treated with kethoxal, so far as their capacity to associate with 16S RNA is concerned. At certain Mg++ concentrations TC 23S RNA is highly susceptible to the nucleolytic action of single-strand specific enzyme RNase I; LC 23S RNA is quite resistant. The Mg++-dependencies of the two species of 23S RNAs for association with 16S RNA are also quite different. The fluorescence enhancement of ethidium bromide due to binding to TC 23S RNA is slightly less than LC 23S RNA. The hyperchromicity of LC 23S RNA due to thermal denaturation is somewhat more than TC 23S RNA. LC 23S RNA has slightly more elliptic CD spectrum than TC 23S RNA. These results clearly show that 23S RNAs present in TC and LC 50S ribosomes are distinct from each other. It has been recently demonstrated in this laboratory that they can be interconverted by the agents involved in translocation and thus appear to be conformomers.

Aldehydes↗
PubMed1984

Kaposi's sarcoma in a 2-year-old child.

A rare case of Kaposi's Sarcoma primarily originating in the oral cavity of a 2-year-old male child with subsequent metastatic spread to the lymph node is presented and the literature reviewed.

Biopsy↗
PubMed1984

Covalent binding of isomeric 7-(2,3-epoxypropoxy)actinomycin D to DNA.

We have examined the ability of 7-(2,3-epoxypropoxy)actinomycin D (EPA) to bind covalently to DNA and to 2'-deoxyribonucleoside 5'-monophosphates in a simple system in vitro. We have observed initially that EPA binds to DNA and deoxymono- and deoxydinucleotides with intercalative or stacking interactions that are characteristic of actinomycin D (AMD). When EPA is incubated (37 degrees C) for a prolonged period (pH 7.4, 6 h) in contact with either DNA or deoxyribonucleotides, it forms covalent adducts. Deoxyguanosine is always the preferred site of reaction by EPA. After enzymatic digestion of EPA-DNA adduct, three deoxyguanosine (EPA-dG) adducts, one major and two minor, were isolated. These adducts are separable from one another and from other deoxyribonucleoside adducts, e.g., EPA-dA and EPA-dC by reverse-phase HPLC. The authentic EPA-dG, EPA-dA, and EPA-dC adducts were synthesized by a chemical reaction of the epoxide in EPA with the deoxyribonucleotides followed by enzymatic dephosphorylation of the products. From the EPA-DNA adduct the EPA-dG adducts accounted for congruent to 2.2% of EPA employed; the remainder of EPA was completely hydrolyzed to an epoxide ring opened diol derivative, DHPA. DHPA binds to DNA by intercalation only and it does not form covalent adducts. Another model analogue of EPA (EPAMDEA) has the same epoxide-substituted chromophore but lacks the peptide lactone functions; it fails to associate with DNA and consequently it shows no covalent binding of its epoxide with DNA. Formation of a noncovalent intercalation complex between EPA and DNA appears to be a prerequisite for the covalent reaction. Presumably because of these dual interactions, EPA demonstrates superior antitumor activities both in human leukemic cells (CCRF-CEM) in vitro and P388 and L1210 cells in mice. The DNA base specific alkylating activity of EPA, which is derived from a combination of the actinomycin D (AMD) structure and the new epoxide function in the molecule of EPA, attributes to EPA a potentially novel pharmacological behavior that is not inherent of AMD.

Animals↗