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Combined treatment of murine leukemia P388 with doxorubicin and platinum(IV)-nitroxyl complex ВС118 administered in low doses improved efficiency of treatment (cure of 83% of animals) without increasing toxicity.

We presented results of monotherapy and combination therapy of transplantable murine tumor models using methionine-gamma-lyase (MGL) and pyridoxine hydrochloride. We studied MGL from Clostridium sporogenes and Citrobacter freundii. We used Lewis lung carcinoma (LLC), melanoma B16, leukemias P388 and L1210 and Fisher lymphadenosis L5178y. Neither monotherapy with MGL nor combination of MGL and pyridoxine demonstrated antitumor activity against P388 and L5178y. In the murine L1210 leukemia model, MGL C. sporogenes injected intraperitoneally in the dose of 2000 U/kg, 11 times with a 12-hour interval increased the life span of mice (ILS=22 %, р=0.035). In the LLC model, the combination of MGL C. sporogenes at a dose of 400 U/kg, i.p., 4 times with a 48-hour interval and pyridoxine at a dose of 250 mg/kg led to tumor growth inhibition (TGI=55 %, р

We studied the effectiveness of cyclic hydroxamic acid CHA-5 against drug-resistant and multidrug-resistant murine P388 leukemia strains. More than 60% mice receiving transplantation of rubomycin-resistant leukemia P388 strain survived after CHA-5 monotherapy; combined therapy with CHA-5 and cisplatin was also highly effective. Vincristine-resistant tumor was highly sensitive to combined treatment with CHA-5 and cyclophosphamide. It should be emphasized that standard antitumor agents were used in very low doses in combination therapy and CHA-5 significantly potentiated their effect.

Leukemia or blood cancer is a disease which marked by abnormal increasing of blood producer`s cells. Chemotherapies which used as anticancer have a many adverse effect and toxicity. The volatile oil of turmeric rhizome (Curcuma xanthorriza) contains sesquiterpene which has an pharmacological activity. The aimed of this research to assay the antiproliferation activity of volatile oil from curcuma rhizome to leukemia P388 cells using MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl tetrazolium bromide) method. The methods were contain of identification of volatile oil (produced from distillation water-steam) using organoleptic test and TLC, and activity test was using seven various concentrations, which were 0.1; 0.3; 1; 3; 10; 30; 100 µg/mL. The result showed that the sample can inhibit leukemia P388 cells with the value of IC50 was 15.5 µg/mL. The volatile oil of Curcuma rhizome has an antiproliferative activity to leukemia P388 cell.Keywords: Curcuma rhizome, MTT assay, leukemia cell P388, volatile oil

The soil-derived bacterium, Streptomyces sp. CJ-5, was cocultured with the mycolic acid-containing bacterium Tsukamurella pulmonis TP-B0596. The combined culture method significantly enhanced the production of the secondary metabolites in Streptomyces sp. CJ-5, leading to the isolation of three novel butanolide chojalactones A-C (1-3), with unusual γ-butyrolactone scaffolds. The complete structures, including the absolute configurations of 1-3, were determined based on spectroscopic data and total syntheses. In methylthiazole tetrazolium (MTT) assays, 1 and 2 showed moderate cytotoxicity against P388 cells.

An interesting natural product chemistry aspect of Fragraea fragrans is that their fruits are richness with ursolic acid and its isomer oleanolic acid (3.05% of dried powder). As our continuous work on these inseparable structural isomeric triterpenes, this paper reports that 51.0% of inseparable 3-oxo-ursolic[3-oxo-oleanolic] acids and 48.6% of inseparable 3-acethyl-ursolic [3-acethyl-oleanolic] acids have already been made from those triterpenes as starting materials of the oxidized and acetylated compounds and evaluated their activity against P388 leukemia cells. The activity of 3-oxo-ursolic [3-oxo-oleanolic] acids with IC50 = 18.6 µg/mL exhibited three-fold more potent against P388 leukemia cell proliferations compared to ursolic [oleanolic] acids with IC50 = 53.5 µg/mL; while the 3-acethyl-ursolic [3-acethyl-oleanolic] acids with IC50 = 37.9 µg/mL showed two-fold more potent then their parent triterpenes (IC50 = 53.5 µg/mL) in the inhibition of P388 leukemia cell growth.

Four new cembrane-type diterpenes; numerosol A–D (1–4); along with a known steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral Sinularia numerosa. The structures of these metabolites were determined by extensive analysis of spectroscopic data. Gibberoketosterol (5) exhibited cytotoxicity against P-388 (mouse lymphocytic leukemia) cell line with an ED50 of 6.9 μM.

Six compounds, KP-1 up to KP-6 were isolated from the methanol extract of the tree bark of Dipterocarpus confertus Sloot (Dipterocarpaceae). The cytotoxic activities of these compounds were evaluated against murine leukemia P388 cells. Result of these examination indicated that KP-2 compound and KP-1 were very active with each IC 50 value of these compounds were 2.25 and 5.1 μg/mL, respectively. While the others were not active against murine leukemia P388 cells.Keywords: Dipterocarpaceae, Dipterocarpus confertus Sloot, isolated compounds, cytotoxic, and leukemia P-388 cell

The payload of antibody–drug conjugates (ADCs) is the warhead of ADCs that kills the tumor cells. Three classes of highly potent toxins including maytansinoids, auristatins, and calicheamicins are currently being employed or pursued in the clinic as the payloads of ADCs. The structures, mechanisms of action, pharmacokinetics, and toxicities of these toxins are reviewed and discussed. The payloads along with the clinically tested ADCs and their therapeutic areas are summarized.

(−)-4-Aza-4-deoxypodophyllotoxin ( 4 ) was synthesized from (−)-podophyllotoxin ( 1 ) through C-ring cleavage, Curtius rearrangement and intramolecular N -alkylation. Analogue 4 showed potent cytotoxicity against P388 leukemia cells.

Summary Five derivatives of melphalan (( S )-4-[bis(2-chloroethyl)amino]phenylalanine), an alkylating agent presently employed as an antineoplastic in humans, were designed and synthesised as potential prodrugs. Their antitumour activity was tested against P388 leukaemia in mouse after acute intraperitoneal or oral administration and compared with that of the parent compound.

P‐Glycoprotein inhibitors, including the nonimmunosuppressive cyclosporin D analog SDZ PSC 833 (PSC 833), have been developed to circumvent multidrug resistance. In the present study, the potential of PSC 833 in reversing multidrug resistance was evaluated in various systemic treatment models with leukemic and solid‐tumor‐bearing mice. Having a relatively wide therapeutic window of daily p.o. doses from 12.5 to 75 mg/kg, PSC 833 significantly improved the antileukemic activity of the anticancer drugs adriamycin (ADM), vincristine (VCR) and etoposide (VP‐16) given i.p. or i.v. against i.p.‐inoculated vincristine‐resistant P388 tumor (P388/VCR). PSC 833 in combination with i.p.‐injected anticancer drugs in optimal schedule and dosage induced apparent cures in some leukemic mice, whereas no cures were obtained with the cyclosporin A/anticancer drug combinations. PSC 833 combined with i.v.‐injected anticancer drugs was highly active, but not curative, against P388/VCR and parental P388 tumors (maximum T/C>175%). PSC 833 in combination with intravenous treatment with ADM showed prominent anti‐solid‐tumor activity against s.c.‐inoculated colon adenocarcinoma 26 and human colorectal adenocarcinoma HCT‐15. Against colon adenocarcinoma 26, the PSC 833/ADM combinations induced cure in two or three of six mice. PSC 833/ADM combinations significantly inhibited the growth of the tumor with maximum percent inhibitions of 83 and 73% in the early and advanced stages of the HCT‐15 tumor models, respectively. The present study demonstrated that PSC 833 is highly active in potentiating the antitumor activity of systemically administered ADM, VCR and VP‐16 against four murine and human tumors with a relatively wide therapeutic window of daily p.o. dose range of 12.5–100 mg/kg.

During 1985-1990 the U.S. National Cancer Institute (NCI) phased out its murine leukemia P388 anticancer drug screening program and developed as the replacement a new in vitro primary screen based upon a diverse panel of human tumor cell lines. For each substance tested, the screen generates a remarkably reproducible and characteristic profile of differential in vitro cellular sensitivity, or lack thereof, across the 60 different cell lines comprising the panel. Several investigational approaches to display, analysis and interpretation of such profiles and databases, derived from the testing of tens of thousands of substances during the past 4-5 years since the NCI screen became fully operational, have been explored. A variety of useful, practical applications of the in vitro screen have become apparent. As these applications continue to evolve, they are proving to be complementary to diverse other anticancer screening and drug discovery strategies being developed or pursued elsewhere. Reviewed herein are some practical considerations and selected specific examples, particularly illustrating research applications of the NCI screen that may be more broadly applicable to the search for new anticancer drug development leads with novel profiles of antitumor activity and/or mechanisms of action.

Chemical investigation of the Dongsha Atoll soft coral Lobophytum crassum has afforded four new cembranoids, crassumols A-C (1-3) and 13-acetoxysarcophytoxide (4). The structures of these isolated compounds were elucidated by extensive NMR and HRESIMS experiments. The cytotoxicity and anti-HCMV (Human cytomegalovirus) activities of 1-4 were evaluated in vitro. Compound 4 exhibited cytotoxicity against A-549 (human lung carcinoma) cell line with an ED(50) of 3.6 μg/mL.

A new class of deoxyribonucleic acid (DNA)-intercalating antitumor agents, novel 9-anilino-2,3-ethylenedioxyacridines (five compounds) have been synthesized and evaluated for activity against P388 leukemia in vivo. A few of them possessed the same potency of antitumor activity as amsacrine (m-AMSA) which is an important antitumor agent in clinical use.

A versatile and efficient synthetic route to 4-demethoxyanthracyclinones has been utilized in the preparation of a number of aglycons having 9-alkyl, 9-(hydroxylalkyl), or 9-carbamoyl substituents. Silver trifluoromethanesulfonate catalyzed coupling of these aglycons with various daunosamine derivatives has yielded a series of novel anthracyclines which have been evaluated as antitumor agents. 9-Alkylanthracyclines 22, 23, 33, and 34 have higher efficacy vs L-1210 leukemia than the parent 4-demethoxydaunorubicin (21), or the natural anthracyclines daunorubicin (1) and doxorubicin (2). 9-(Hydroxyalkyl) derivatives have in most cases high efficacy but are slightly less potent than 21. 9-Methyl analogue 22 has higher efficacy vs P388 leukemia than other anthracyclines tested, while 9-(hydroxymethyl) derivative 37 retains similar efficacy to anthracyclines 1, 2, and 21 but is considerably more potent. The N-substituted 9-carbamoylanthracyclines are devoid of antitumor activity.

Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycine derivatives were more potent than acronycine itself when tested against L1210 cells in vitro. Four selected acronycine derivatives (17, 19, 21, and 22) were evaluated in vivo against murine P388 leukemia and colon 38 adenocarcinoma implanted in mice. All compounds were markedly active against P388 at doses 4−16-fold lower than acronycine itself. Against the colon 38 adenocarcinoma, the three compounds 17, 21, and 22 were highly efficient. 1,2-Diacetoxy-1,2-dihydroacronycine (17) was the most active, all the treated mice being tumor-free on day 23.

A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo.

The study was performed to investigate the effect of ascitic fluid globulins of tumor on tumor growth and life span of mice. The globulins are shown to shorten the life span of Ehrlich tumor mice from 86.8 to 61.8 days, to increase 3-5-fold the growth rate of Ehrlich carcinoma and P388/DOX tumor. It was found that globulins of ascitic fluids and serum globulins of tumor have equal effects of tumor growth. It is proposed to use globulins of ascitic fluid to study the globulin role in tumor growth.

The A ring of the clinical antitumor agent, etoposide, was opened to a protected 6,7-diphenol which was derivatized to form a number of new analogs. These compounds displayed activity inferior to etoposide when evaluated against several tumor cells line in vitro and against murine P388 leukemia in vivo .

A predictive design is explored with nitroxyl labeled derivatives, and other congeners of alkylating drugs TEPA/Thio-TEPA, CCNU/MeCCNU, and Streptozotocin/Chlorozotocin. The design is based on correlations of lipophilicities of these drugs with their antineoplastic activities in vivo against the murine lymphocytic leukemia P388. Some results are also included of evaluations using the nturine lymphoid leukemia L1210. therapeutic indices than those of the parent drugs which are in clinical use, and, hence, warrant further studies. Several of these compounds possess considerably higher

At Southern Research Institute, a series of in vivo drug-resistant murine P388 leu-kemias were developed for use in the evaluation of crossresistance and collateral sensitivity. These in vivo models have been used for the evaluation of new compounds of potential clinical interest. Crossresistance data coupled with knowledge of the mechanisms of resistance operative in the drug-resistant leukemias may identify useful guides for patient selection for clinical trials of new anti tumor drugs and noncrossresistant drug combinations.

Tricalysia dubia (Rubiaceae), an evergreen shrub or tree, is widely distributed in Taiwan, the southern parts of China and Japan. From the leaves of this plants, unique rearranged ent-kaurane glycosides A – G, and the ent-kaurane glycosides H – O, have been isolated. In our presentation, six rearranged ent-kaurane diterpenes, tricalysiolides A – F [1], tricalysiamides A – D [2], tricalysiolide H, tricalysiones A and B [3], and a known diterpene, cafestol from the wood of this plant are reported, especially their cytotoxic activity against P388 leukemia cells in mice as well as the structure elucidation using spectral analyses and chemical methods. References: [1] Nishimura, K. et al. (2006), Tetrahedron, 62, 1512. [2] (2007) J. Nat. Prod., in press. [3] (2007) Tetrahedron, in press.

L1210 and P388 leukemia models have been extensively used over the last 50 years. The models are rapid, reproducible, and relatively inexpensive (in comparison to human tumor xenograft and transgenic models). However, as with any experimental animal tumor model, there are limitations. Neither leukemia is a satisfactory model for either human cancer in general or human leukemia in particular. Despite the limitations of murine leukemia models, these models have been useful in making progress in anticancer drug development, in the development of a number of therapeutic principles, and in understanding the biologic behavior of tumor and host. These models are still useful today in conducting detailed evaluations of new candidate anticancer drugs (e.g., schedule dependency, route of administration dependency, formulation comparison, analog comparison, and combination chemotherapy). The greatest utility of murine leukemias today is derived from evaluations of drug-resistant sublines for crossresistance and collateral sensitivity. Crossresistance data, coupled with knowledge of resistance mechanisms operative in drug-resistant leukemias, may yield insights into mechanisms of action of agents. Similarly, crossresistance data, coupled with mechanisms of action of various agents, may yield insights into resistance mechanisms operative in drug-resistant leukemias. Furthermore, crossresistance data may identify potentially useful guides for patient selection for clinical trials of new antitumor drugs.

The basis for proceeding with development of an anticancer agent has historically resulted in part from the capacity of the agent to inhibit tumor cell proliferation either in tissue culture (in vitro) or in animals (in vivo), without specific reference to a molecular or cellular target of action. Indeed, the potentially useful effects of the vast majority of agents currently approved for use as safe and effective as oncologic therapeutics in humans were initially detected by their favorable performance in mouse models of human cancer. This chapter provides an overview of the types of mouse models used in cancer drug discovery and development, their strengths and limitations, how to interpret them, and caveats in the consideration of results from commonly used murine model studies. The algorithm currently in use at the National Cancer Institute (NCI) in the United States is presented. This chapter is meant to be a practical, working summary of practice rather than a comprehensive review of the topic. For the latter, the reader is encouraged to seek more encyclopedic treatments (1–3, among others).

1. N. N. II'inskik1% M. A. Medvedev, S. S. Bessudnova, et aL, Mutagenesis in Va~ous Functional States of the Organism [in Russian], Tomsk (1990). 2. Yu. Ya. Kerkis, Usp. Sovr. Biol., No 1, 344-350 (1940). 3. M. E. Lobashev, Vestniic Leningrad. Gos. Univ., No 3, 346376 (1947). 4. G. Selye, The Stress of Life, McGraw (1978). 5. S. V. Seredenin and A. D. Durnev, Khim.-Farm. Zh., No_ 4, 395-399 (1985). 6. C. E. Ford and Y. L. Hamerton, Stain Technot., 31, 247 (1956). 7. W. Smidt, in: Chemical Mutagens, Ed. A. Hollander, Vol. 3, New York-London (1976), pp. 31-53. 8. S. Walles, 21st Ann. Meet. EEMS, Abst. Book (1991), pp. 10-46.

Transplantable animal tumors have been associated with the discovery of most clinically active anticancer agents. They are still useful today in conducting detailed evaluations of new candidate anticancer drugs. Three protocols relating to transplantable experimental tumors are described in this unit. Included are the intravenously-implanted murine P388 leukemia, the subcutaneously-implanted murine B16 melanoma and two examples of subcutaneously-implanted human tumor xenografts, the LX-1 (lung) and MX-1 (breast) tumors.

Saccharothrix aerocolonigenes ATCC 39243 produces an indolocarbazole antitumor agent rebeccamycin under submerged fermentation conditions. Adding DL-6-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the formation of two novel indolocarbazoles, fluoroindolocarbazoles A and B. Feeding DL-5-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the production of a novel indolocarbazole, fluoroindolocarbazole C. These fluoroindolocarbazoles have been isolated from culture broth and purified to homogeneity by vacuum liquid chromatography and column chromatography. All three fluoroindolocarbazoles are more potent than rebeccamycin against P388 leukemia by ip route in murine model.

Treatment of P388 leukemia cells with poly-DL-lysine (Poly-lys) considerably increases the binding of colloidal chromic phosphate (32P). This augmentation of the number of particles that are bound is in direct relationship with Poly-lys concentration, and very significantly with its degree of polymerization. Treatment with Poly-lys molecular weight 77,000 shows a 100% increase of binding with 200 μg and of 50% with 100 μg. Poly-lys M.W. 8,000 presents no significant increase, and for the other molecular weights the binding is intermediate.

Phosphonylmethoxyalkylpurine analogues were evaluated for their antitumor activity in murine tumor models. Three compounds, (S)-9-[(3-hydroxy-2-phosphonylmethoxy)propyl]adenine (HPMPA), 9-[(2-phosphonylmethoxy)ethyl]adenine (PMEA), and 9-[(2-phosphonylmethoxy)ethyl]guanine (PMEG) were modestly active with treated versus control (T/C) values of 125%-175% versus intraperitoneal P388 leukemia, but were inactive versus intravenously implanted P388. The most active and most potent of the three was PMEG, which was also evaluated against subcutaneously (SC) implanted B16 melanoma. In confirmatory experiments, optimal therapy with PMEG yielded reproducible increases in life span (T/C values of 164%-170%) and delays in primary tumor growth (7.3- to 13.0-day T-C values). PMEG is representative of a new class of antitumor antimetabolites heretofore recognized only for their antiviral properties.

Although rebeccamycin exhibits significant in vivo antitumor activity against P388 leukemia and B16 melanoma, its limited solubility in aqueous media posed some problems in further evaluation. In order to find more water-soluble analogues wa have carried out structural modifications of rebeccamycin and in this communication we report some of the promising analogues

Diphenylantimony(III) and diorganotin(IV) derivatives of dithiophosphorus ligands, i.e. Ph2SbS2PR′2 (R′ = Ph, OPr-i) and R2Sn(S2PR′2)2 (R = n-Bu, Ph, R′ = Ph; R = Ph, R′ = OPr-i), have been screened against P388 leukemia in mice. All the compounds showed marginal activity towards this tumor system, some of them increasing the life span of the animals with more than 20%. The best results were obtained with (di-iso-propylphosphorodithioato)diphenylantimony(III) which exhibited a T/C value of 136%, at a dose of 5 mg/kg, administered on days 1,2 and 3 after tumor transplantation.

We have reported that dimethyl sulfoxide (DMSO) and antineoplastic agents exhibit synergistic cytotoxicity against human tumors in vitro. This study was undertaken to investigate this effect in vivo. Groups of mice were given intraperitoneal (i.p.) injections of P388 leukemia cells. Groups were treated with i.p. injections of either saline, DMSO alone, mitoxantrone hydrochloride (DHAD) alone, methotrexate alone, DHAD in DMSO or methotrexate in DMSO. Combinations of DMSO and DHAD produced 46-61% increases above expected survival, demonstrating synergistic cytotoxicity in vivo. Following confirmatory animal studies, trials utilizing i.p. delivery of antineoplastics in DMSO as treatment for peritoneal tumors should be undertaken.

Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2 mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.

Yuanhua, Flos Genkwa, is the dry flower buds of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae) collected in spring before blossom. It is officially listed in the Chinese Pharmacopoeia and is a traditional Chinese medicine used as a diuretic in treatment of ascites, edema, and asthma. Externally it is used against scabies and ulcer. In addition, the root bark of D. genkwa has also been used as a diuretic, especially in treatment of ascites in late-stage schistosomiasis.

Seventy novel benzoylphenylurea compounds were synthesized and their antitumor activities were examined in vivo against P388 leukemia. N-(2-Nitrobenzoyl)-N'-[4-(2-pyrimidinyloxy)phenyl]ureas showed the highest antitumor activities when dosed intraperitoneally or orally. Their structure-activity relationships were examined with particular focus on the position and the variety of subsitituent on each aryl ring.

A predictive design is explored with nitroxyl labeled derivatives, and other congeners of alkylating drugs TEPA/Thio-TEPA, CCNU/MeCCNU, and Streptozotocin/Chlorozotocin. The design is based on correlations of lipophilicities of these drugs with their antineoplastic activities in vivo against the murine lymphocytic leukemia P388. Some results are also included of evaluations using the nturine lymphoid leukemia L1210. therapeutic indices than those of the parent drugs which are in clinical use, and, hence, warrant further studies. Several of these compounds possess considerably higher

α-[N,N-[bis(2-hydroxyethyl)]-amino]-N-(o-methoxyphenyl)pyrrolidin-2,5-dione (I), an intermediate in the synthesis of pyrrolidine-dione-N-mustards, did not exhibit antitumour activity against P388 lymphocytic leukemia, Sarcoma 180 (ascites) and Ehrlich (ascites) carcinoma tumours. The effect of co-administration of (I) with established anticancer drugs was studied against these murine tumours. The activity of 5-fluorouracil against Sarcoma 180 (ascites) and Ehrlich (ascites) carcinoma was significantly enhanced by co-administration with (I). Other anticancer drugs, when co-administered with (I), did not show any enhancing effect.

The efficacy of dipyrone to modulate antitumor activity of mitoxantrone (MTN) and doxorubicin (DOX) was studied in vivo in mice bearing P388 murine lymphocytic leukemia sensitive (P388/S) and resistant P388/DOX) to DOX. P388/DOX-bearing mice demonstrated marginally higher sensitivity to dipyrone at 200 mg/kg when compared to P388/S-bearing mice. However, dipyrone could significantly enhance the antitumor activity of MTN and DOX in both P388/S and P388/DOX-tumor-bearing mice. MTN was cross-resistant to P388/DOX.

The synthesis of a series of 1-aryl- N,N′ -di(1,3,4-thiadiazol-2-yl)methylenediamines is reported. The compounds are obtained by means of reaction between 2-amino-1,3,4-thiadiazole and aromatic aldehydes. The title compounds were evaluated against the leukemia P388 tumor system in mice and some of them were found to be active. 1-(2,6-Dichlorophenyl)- N,N′ -di(1,3,4-thiadiazol-2-yl)methylenediamine 1 , whose significant activity against P388 leukemia was reported in a previous paper, was tested against other experimental tumors. It exhibits significant activity against L1210 leukemia and M 5076 ascitic sarcoma.